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A career in biotech?

May 4, 2013, 11:14 am
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I'm a GCSE student but I like planning ahead... I think I want to go into biotech since it gives a meaning to my career as I will help making peoples lives better...

I'd say I'm quite strong in both biology and chemistry because of my critical thinking skills and also my ability of visualising and understanding concepts instead of memorising them. I am also quite strong at business studies as I always try to think of business realistically.

I thought of going into medical biotech, but just recently found out medicine is not my thing. Firstly as an int student I won't have enough money to study 6 years on undergraduate level, also I feel like medicine is not really that important 'cause people will die eventually anyway.

Generally, I want to work in a biotech company for 15 years, then own one as an entrepeneur. Any ideas on which industry should I work on? (I'm quite sure i'll be stronger in genetics and animal biotech)

Also, for my A levels, except for biology, chemistry and maths, which subject should I take?(Business/economics/psychology) I think I will be good at all three and all three of them can help me as a future biotech company manger... My college has good teachers in all three subjects as well.

Thank you very much for your advices...
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Stem Cell Treatments to Relieve Symptoms in Down Syndrome

May 4, 2013, 11:18 am
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Down syndrome is a genetic disorder caused by the abnormal presence of the entire or a part of an extra chromosome 21. The disorder is named after John Langdon Down, a British doctor who described disease in 1866. The disease is sometimes referred to as “mongolism” and “Mongolian idiocy.” The typical patient suffering from Down syndrome has a total of 47 chromosomes in all the somatic cells of the body. Such an abnormality accounts for the impaired growth and development of the child.

Down syndrome is the leading genetic cause of mental retardation. Statistics report the incidence of Down syndrome to be 1 per 800 live birth babies, making it one of the most frequently inherited chromosomal disorders. These statistics are profoundly influenced by the age of the mother at the time of birth.

People with Down syndrome have very distinct common physical features, which include a flat face, a almond-shaped eyes, epicanthic folds of the eyelids, a small broad nose, abnormally shaped ears, a large protruding tongue, and shorter limbs, a larger-than-normal space between the first and second toes, poor muscle tone... They have also increased risk for respiratory infections, congenital heart defects, gastrointestinal obstruction, and obstructive sleep apnea, thyroid dysfunction, hearing loss, leukemia and Alzheimer’s disease.

Diagnose

There are two types of tests check for Down syndrome during a woman's pregnancy.

Screening test indentify a mother who probably carries a baby with Down syndrome. The most commonly used screening tests are the double and triple screen, also known as triple test, multiple marker screening and alpha fetoprotein plus. Screening may be a maternal blood test done in the first trimester with a special ultrasound to measure the thickness at the back of the baby’s neck (called nuchal translucency). And it can be also done a maternal blood test in the second trimester without the ultrasound. However, screening tests cannot diagnose Down syndrome or other genetic disorder. The diagnosis must be confirmed by a chromosome study (karyotype).

Diagnostic test confirm a positive result identified in a screening test. The most common are amniocentesis, chorionic villus sampling (CVS), and percutaneous umbilical blood sampling (PUBS). Each of them takes a sample from the amniotic fluid, placenta, or umbilical cord to examine the baby's chromosomes and determine an extra chromosome 21.

Therapy

Until now there was no cure for Down syndrome. Only physical therapy and speech therapy could be helpful and made life easier for patients. Following the medical problems associated with the disorder could often improve quality of life.

Stem Cells Research

A large number of Down syndrome children had already been treated with Stem Cell therapy. The results concluded that there is a statistically significant improvement in height, concentration, IQ, speech, motor skills and immune system. Stem cell therapy carried out at an early stage the typical features of Down syndrome become less pronounced and the immunological deficiencies are corrected. This syndrome is one of many conditions which have responded dramatically to stem cell therapy.

Scientists used stem cells from the developing human brain, and grow them in spherical aggregates called neurospheres. They used neurospheres from post-mortem fetuses (with and without Down syndrome), and biochemically induced to form nerve cells. The RNA proteins were extracted from the neurospheres and compared with the RNA proteins from normal neurospheres. After all experiments, it was found that one specific protein was absent from te neurospheres of patients with Down syndrome. The SCG10 gene was relatively or absolutely functionally deficient. They also discovered that certain other genes were also underexpressed, such as L1, Synapsin, and ß4- tubulin. The neurons from the defective stem cells were shorter, irregular, had misshapen axons, and fewer dendrites projected from the main body of the neuron when compared with the control.

Stem cell research discovered a substantial disorder in the genetics of the development of neurons that begins in the earliest stages of formation of the embryo with Down syndrome, resulting form a disruption of expression of certain genes of the neurons.

Cord Stem Cells Treatment

Cord blood is collected because it contains stem cells which are genetically unique. Umbilical cord blood contains stem cells of blood, a very limited amount of mesenchymal cells, and immune cells. These stem cells, at modern time, are very used for the research, how to induce regeneration in various neurological disorders, such as also Down's syndrome. Human fetal stem cell transplants are a new area.

New studies have shown that mesenchymal and CD34 stem cells from umbilical cord blood in combination with grow factor, neurotropic and antioxidant supplements, and stem cell nutrition offers the potential to increase brain tissue development and stop the production of the abnormal protein which interferes with such development.

Patients with Down syndrome had already been treated with cord driven stem cell therapy before the age of 15. The results concluded that there is a statistically significant improvement physical and mental characteristics. The typical features of Down syndrome become less pronounced and the immunological deficiencies are corrected, when treatment is applied earlier.

Umbilical cord stem cells hold promise for reducing some of the symptoms of Down syndrome. This is a new, exciting frontier for human umbilical cord stem cells.

Research efforts aspire to examine the role of individual genes developing Down syndrome and to determine why those individuals with this condition are particularly vulnerable to diseases like leukemia and autoimmune disease. Stem cell research in Down syndrome offers hope in detecting individual genes, which are responsible for complex conditions, such as hypertension, diabetes, and to create artificial chromosomes for gene therapy. There is not a specific cure for Down syndrome at present, but researchers believe that gene therapy will enhance therapeutic options for such people, in the future. A patient with Down could benefit from drugs that could help regulate proper gene expression. At the pace of present research, the future looks very hopeful.
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Influence of The Heart Cells on Amniotic Stem Cells and Newest Scaffold Research

May 4, 2013, 11:21 am
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Amniotic fluid has a population of stem cells which have markers expressed characteristic for embryonic and mesenchymal stem cells. These amniotic fluid- derived stem cells can differentiate across all three germ layers, they don’t have tumorigenic potential like embryonic stem cells and they can maintain prolonged non differented stem cells like embyonic stem cells. This is very important, because amniotic fluid could provide an autologous source of the cells for tissue engineering.

Latest studies have shown that these stem cells have huge potential in heart therapies. However, understanding of these studies is needed. The important thing is to separate things what stem cells can do with heart cells, and what they cannot. Researchers at Rice University and Texas Children's Hospital have founded that communication between these two cell types is possible. Mature heart cells and stem cells have ability to create electrical couplings between themselves like heart cells in heart tissue. During this electrical connection, stem cells cannot transform themselves to mature heart cells, and this is limitation of this method. Patients with Tetralogy of Fallot have biocompatible patches surgically placed across right ventricular outflow tract of the heart.

Procedure of stem cell implementation and scaffold types

Procedure of stem cell transplantation cannot be done without special scaffold patches. Idea of biocompatible patches seeded with stem cells is brilliant, because scaffold patches would ideally support stem cells implementation.

Current patches are made from synthetic fabrics or they can be obtained from cows or from patient himself. This kind of treatment is not bad, but it has limitations. These patches are more like plastic, and they don’t have ability to grow together with patients. Therefore, they have to be replaced in correlation with patients growth. Also these patches are implanted in heart and it's good for heart contraction. However, electrical signals have to go around this dead tissue. This implicates that heart has less contraction power and surely it can lead to heart failure or arrhythmias and fibrillations. When we summarize these facts we can conclude that these scaffolds have high short- and medium- term success rate and, unfortunately, long- term complications.

Newest scaffold research

Researchers have tried to discover the perfect scaffold. This perfect scaffold should be strong enough for heart contractions, porous enough to allow migration of the new differentiated cells, tough enough, but also able to degrade itself after certain amount of time. The newest discovery is scaffold which is created of polycaprolactone and double layer made from mixture of chitosan and gelatin. Researchers believe that this could be a tremendous discovery, because this scaffold has shown good properties. When in water, this scaffold degrades, but if it is placed in human body, it will degrade very slowly, over a month. This scaffold should be strong for a certain period of time that will help heart muscle to recover and to take over support process. However, many years of testing await scientists before they begin human trials, but they are very optimistic, and they expect positive results.

Directions in future researches

If scientists want to implant perfectly grown tissue that will not be rejected, they have to find out how intercellular signals can guide transformation of an amniotic stem cell into a heart cell. Research on the rats have shown that stem cells can only communicate with heart cells through channels in their membrane that provide exchange of the ions and small molecules.

A certain part of scientists suggested that physical contact between amniotic stem cells and heart cells have positive influence in differentiation of stem cells. However, scientists on the newest researches have proved that this is not correct. The newest researches showed that previous claim was incorrect because they saw only fusion of amniotic stem cell and heart cell. That is what this research was based on. Researchers wanted to see if amniotic stem cells could have characteristics of heart cells if fusion between these two cells were not allowed. They revealed results, and results have shown that it is not possible to convert an amniotic stem cell into a heart cell, but certain change in gene expression was present. The finding was connection between stem cells with a gap junction connections. This gap junction connection can transfer some really small molecules and electrical ions. These ions and molecules can diffuse between two cells connected with this junction. However, this diffusion is not possible when amniotic stem cells are not in connection with heart cells.

This research has unique approach, because other researchers approach is directly injection in heart tissue. This other approach is studying how directly injected amniotic stem cells can help in treatment of heart attack recovery. Researches from the Rice University and Texas Children's Hospital are not enthusiastic about this other research, because they think that this research will show them role of paracrine signal effects. They think that stem cells directly injected can help only in stabilization of the cells, but they cannot differentiate and create new heart tissue.

Conclusion of the research

The biggest discovery of this research is fact that cell contact between amniotic stem cells and heart cells cannot induce transformation of the stem cells, but it produces more functional gap junction connection than amniotic stem cell cultures without cell contact. However, if we want a bigger results right now, probably additional cues and maybe tighter connection between stem cells and heart cells, or maybe fusion, is required.

The ease of obtaining this type of stem cells, widely multipotent nature and rapid proliferation rate make this cell type promising source for future researches in tissue engineering.

Researchers are sure that there are plenty of methods to get amniotic fluid- derived stem cells differentiate into desired tissue for medical uses, and this research has revealed only small part of stem cell differentiation.
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Medicinal Power of Human Urine!

May 4, 2013, 12:07 pm
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The title of the article itself must have caught a good deal of your attention! Most of you probably might have been getting a yuck! feeling imagining the consumption of Human Urine as a Medicine! But it's true! Human Urine is more than just an excretory-waste liquid thrown out of the body a couple of times a day.
Rather, there are companies making Billions of dollars by selling drugs extracted from Human Urine, and there are instances in the world where people have been cured of diseases like chronic cystitis drinking their own Urine! So, the focus of this article is to deliver insights into the concept of Human Urine as a Medicine.

"Urine is Sterile Liquid!"

Firstly, one should get rid of the notion that Urine might be containing a lot of contamination/microbes. Human Urine is aseptic and ultra-sterile. Only those humans, suffering from some UTI (Urinary Tract Infection) tend to excrete microbe infected urine. Otherwise, Human Urine is free of infectious organisms. So, this removes one of the key hurdles towards use of urine as a medicine.

Human Urine is Free of Toxic Metabolites
Another important fact one should be aware of is that " Human Urine is Free of Toxic Metabolites" It's the job of Human Liver to detoxify the blood (not of kidneys) of toxic metabolites generated upon digestion of food/medicinal intake. The toxins are then excreted out of the body as fecal matter (not in urine). Urine is rather produced in the kidneys, where the job of nephrons (cells, functional unit of kidneys), is to mediate the filtration of blood to rid it off excess urea, salts, Zinc, Iron, Calcium, Manganese, Magnesium, Some Pigments, vitamins, Hormones, Amino Acids,Glucose, and water, to maintain Homeostasis (a condition of balance) in the body.

An Important Point About Urine
It's just a liquid secreted by body to expel excess "important substances" out of the body. Almost every component excreted in urine has a role to play in human body, but it's excreted out only because body has a particular threshold requirement of every element, any amount in excess is needless, and is excreted if that cannot be stored (Best example being vitamins and hormones, which are never stored in body. If they are in excess, they will be coming out of the body in Urine.

Medicinal Components in Urine
Needless to say, almost every component in human urine has a potential to be a medicine (depending upon the cases/deficits). Here are a few categories:

A. Enzymes
Pharma companies are always hankering after the ways to extract enymes/proteins out of the human urine. They are one of the billion dollars components of the urine. Best example to cite this is " Urokinase" an enzyme extracted from urine which is a miracle drug for dissolving blood clots in coronary arteries.

B. Urea
One of the key components excreted out of body in urine. Owing to it's moisturizing capabilities, it's a key constituent of world renowned creams/lotions. Most of you must have used or known someone having used MURINE EAR & EYE DROPS? Well, they are used to moisturize the eyes/ears (rest goes needless to say I guess).

C. Hormones
Another component(s) of Urine with a billion dollar market cap! All the excess hormones like testosterone, FSH, LH etc are secreted in urine. And, each of these is a routine part of Hormone therapy of billions of people round the globe! A popular fertility drug obtained from urine, named "Pergonal" which is a mixture of follicle-stimulating hormones (FSH) and Luteinizing hormone (LH) had a starting market of $800 million in 1992 only. One can easily imagine the size of market it might have covered till date!

D. Vitamins and Amino Acids
Alanine, Arginine, Ascorbic acid, Biotin, Folic acid, Glutamic acid, Glycine, Inositol,Lysine, Methionine, Nitrogen, Pantothenic acid, Phenylalaline, Riboflavin, Tryptophan, Tyrosine, Vitamin B6, Vitamin B12 are some of the common excretory products of urine, but all of them indispensable for the body.
The reason behind Bear Grylls' (Man Vs Wild, Discovery Channel) recommendation for taking your own urine when there's nothing else to survive on, is very valid. Your urine has a lot to contribute to your body in extreme situations of drought/food shortage!

E. Tendency to Free an Allergic Person from Allergies
Research has proved that due to the fact that urine has the antigen receptors responsible for causing allergic responses in a person suffering from allergy to a particular antigen, if the person is made to drink his/her own urine, he/she may develop antibodies against the antigen that can rid him/her off future inflammations! (An immunity to allergy!)

There's a lot one can explore about the medicinal properties of human urine (in India, people are rather obsessed for Cow's Urine too), this was just an attempt to bring a fact into picture.

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Nano-particles Provide Long-lasting Blood Glucose Control

May 5, 2013, 6:46 am
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Diabetes mellitus is a disorder in which the body is not able to properly process sugar. This normally results from insufficient insulin, a hormone that helps tell cells to take in sugar from the blood stream. It is important for patients with diabetes mellitus to maintain appropriate blood sugar levels in order to minimize the risks associated with long term high blood sugar, including peripheral neuropathy, kidney problems, and heart disorders. There are two major forms of diabetes mellitus. In Type I diabetes mellitus, the patient’s immune system attacks pancreatic cells responsible for producing insulin. In Type II diabetes mellitus, the patient is either unable to produce an adequate amount of insulin, or his or her cells become insulin resistant and do not respond efficiently to the hormone.

Type I diabetes mellitus requires regular insulin injections to make up for the lost hormone producing cells. Type II diabetes mellitus can sometime be treated with exercise and diet, but can often require insulin and other medications. Insulin injections are required at least daily, as insulin is a protein and is broken down by the body. In addition, as blood sugar levels change in response to meals, different doses of insulin may be required. There are no current long term treatments available for diabetes mellitus- daily lifestyle adjustments are required to maintain proper blood sugar levels. Diabetes mellitus is a chronic condition, with no cures available to stop the disease. Options that could provide control of blood sugar levels for days or even longer are needed to help improve patient compliance and prevent complications from diabetes mellitus.

Recent animal tests performed by teams of researchers from a group of institutions from North Carolina State University, the University of North Carolina Chapel Hill, Children’s Hospital Boston, and the Massachusetts Institute of Technology have shown that a new strategy could help provide insulin to the body’s cells for several days, after only one injection. The study involved the use of nano-particles that are injected into the bloodstream. The nano-particles were able to sense blood glucose levels, and release appropriate amounts of insulin in response to changing sugar concentrations. The nano-particles are composed of insulin that has been coated in glucose oxidase enzymes and modified dextran. When blood glucose levels begin to increase, the glucose oxidase enzymes will convert the glucose into gluconic acid, which breaks down the dextran and releases the insulin. This system was able to successfully control blood glucose levels in mice for up to ten days. The nano-particles are coated in biologic materials with either a positive or negative charge. When these are injected under the skin, they form a network, which holds the nano-particles together and prevents them from circulating throughout the body. This network functions in a manner similar to the pancreas, releasing insulin as blood glucose levels increase.

All of the materials used to build the nano-network are biologically compatible. This means they will be processed by the body and removed by the excretory system, without interacting with other systems. This is important, and means that the nano-particle insulin system may quickly be moved into human clinical trials without requiring major modifications. Safety is always a major concern when new therapeutic strategies are introduced to human studies. By using these biologically compatible molecules, the possibility of negative reactions is significantly minimized, and the therapy itself will be more beneficial.

A major benefit of the nano-particle insulin distribution system has to do with its ability to sense and respond to changing blood glucose levels. Many patients with diabetes mellitus require insulin injections to help control blood sugar levels. However, the amount of insulin injected must be determined by the patient in response to recent food consumption and glucose readings, and this is a very imprecise science. While most patients quickly develop a method for determining how much insulin to take, they are still relying on human calculations, which can be faulty. Administering too much insulin can cause dangerously low blood sugar levels. Too little insulin can result in blood glucose levels remaining too high. Both of these conditions are of serious concern. The nano-particle insulin delivery system takes the guess work out of insulin administration. This could greatly improve blood sugar management in diabetic patients, and improve quality of life.


References:
http://www.sciencedaily.com/releases/201...114716.htm
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Alchemic Microbes - Gold Producing Bacteria

May 5, 2013, 8:17 am
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The term Alchemy is conventionally associated with matter transformation (especially base metals into Gold!). And, when microbes start doing the job of transforming base metals into Gold, it won't be fair if we don't call them Alchemic! So, the focus of this article is to bring into picture the exceptional & radical field of Microbial Alchemy.

The worth of Gold is not an alien fact for anyone around the world. Mining the gold from far-flung sites needs a lot of patience, resources and man-power. And, considering the fact that most of the gold resources have depleted or are at the verge of it, the need for detecting the new sites and better purification strategies has been felt quite strongly in recent times.

Recently in 2012, Researchers at Michigan State University demonstrated a powerful finding wherein a bacteria named Cupriavidus metallidurans could survive on toxic gold chloride (and rather metabolizes it), producing tiny nano-particles of Gold upon reduction of Gold Chloride during respiration!
Here's a video link to the exceptional finding's details:



Though, there are numerous other scientific groups working on the same field of Microbial Alchemy, the finding by the scientists at MSU, and the sharing of the research's efficiency with world has triggered the scientific pursuit in this filed to new levels. According to Anirban Roy Choudhury of IMT (Institute of Microbial Technology) Chandigarh, India, marine water is the richest source of alchemist microbes, owing to the fact that it harbors extreme conditions of high pressure, salinity, low temperatures, variety of metallic compounds etc which could favor the habitation of extremophiles. He claims to have isolated a very effective and fast gold synthesizing strain of Marinobacter pelagius along with the efforts of his team in isolating various species of alchemist bacteria from seas. Acidithiobacillus thiooxidans is another species of bacteria brought into spotlight by scientists from University of Western Ontario in London.

Huge Prospects:

The prospects of microbial alchemy are huge. And, one should realize that it's not limited to just Gold. Literature is filled with instances of microbes that thrive on Ferrous sulphates, Copper Sulphates, Zinc Sulphates etc, such microbes can pave the way for metal mining, regardless of the nature of metal targeted. Each species has it's own prospects for a unique metal.
The applications may be as follows:

A. METAL SENSING
Exhaustion of metal/compounds from the currently known sites has been a big concern. These new findings can enable the synthesis of an efficient bio-sensor for detecting the sites of metals like Gold. And, a rapid prospect in this field would be to use these organisms as Bio-indicators of the possible gold/metal rich site.

B. EFFICIENT PURIFICATION
Though, synthesizing quantifiable amounts of gold from the metabolic process of these bacteria might be highly laborious and complex in terms of the requirement of the scale (as currently the findings suggest only nano-particles of gold being synthesized by the bacteria), but the fact that the gold-nanoparticles synthesized by bacteria is even more pure than the 24-carat gold grains, it suggests the ultra-efficiency of the bioprocess involved in synthesizing the gold.
So, finding a way to genetically modify or improve the strain's character to synthesize greater amounts of gold followed by an appropriate scale-up can lead to a radically new way of synthesizing ultra-pure gold (and other metals too.)
Undoubtedly, it's a neo-alchemy! And a beautiful example of merger of two vastly deviant fileds of microbiology and alchemy. The future is indeed bright in this field, and hope, next time we go out to a jeweler for buying a gold ring, he might convince us about it's purity by the name of the bacteria concerned!

Some References (suggested readings):

Johnston, C. W. et al. Nature Chem. Biol. doi:10.1038/nchembio.1179 (2013).

http://msutoday.msu.edu/news/2012/gold-l...-strength/

http://genomebiology.com/content/pdf/gb-...ws1020.pdf



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Using Math to Help the Immune System Fight Cancer

May 5, 2013, 10:35 am
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T cells and B cells, the white blood cells of the adaptive immune system that help fight infectious agents and cancerous cells, have an amazing repertoire of proteins they can make. There are hundreds of thousands of cell surface receptors that T cells and B cells can make in order to recognize the huge variety of antigens the host is presented with. This is an amazing accomplishment, given that the human genome only has about twenty thousand unique genes. Each T cell or B cell is capable of making only one receptor, specific to one particular antigen. In order to make the huge variety of receptors needed for these adaptive immune cells, different portions of the gene encoding the receptor are combined together the make the receptor. For example, in human T cells, most T cell receptors (TCR) are composed of two recombinant chains, an α chain and a β chain. The α chain is made by combining two random segments, one called a V segment, for variable, and the other a J segment, for joining. The β chain is made by combining a random V segment, a random D segment, and a random J segment. The two randomly made chains will join together to form the final TCR. There are many possible V, D, and J segments that can be combined together for each chain, and the pairing of the α and β chains is random. This ensures a very high diversity of TCRs in the human host, so that a huge variety of pathogens can be recognized and killed by the immune system.

After the T cell has encountered antigen through its TCR, the T cell will then replicate rapidly in response. This is called clonal expansion, because all of the new T cells will have the same TCR. The T cell will work to kill the offending pathogen. After the pathogen has been removed from the host, the T cells will decrease to lower numbers again. Some of the clonally expanded T cells will remain as memory cells, which can quickly be activated and replicate if the antigen is encountered in the future. This is how a memory response develops in the host. The memory T cells help form the TCR repertoire, which is the collection of TCRs in the host.

The random recombination of V, D, and J segments, and random pairing of α and β chains means that different individuals will have differing repertoires of TCRs. This means that a TCR from one individual that recognizes a specific antigen may differ from the TCR of another individual recognizing the same antigen. However, because the antigens are the same, it is expected that certain portions of the TCR will also be similar between these individuals. Scientists from Virginia Commonwealth University Massey Cancer Center have recently begun characterizing the T cell repertoire in volunteers in order to analyze these patterns, which are called fractals. Fractals are patterns that can be found in nature, that repeat themselves over a variety of scales. These repeated patterns only need to be similar to each other, not completely identical.

By examining the fractal patterns among TCRs, researchers hope to find connections between the receptor being produced by the T cell, and the antigen being recognized. They hope to use this information in selecting appropriate donors for cancer patients receiving bone marrow transplants. By analyzing the fractal patterns among T cells, researchers want to find specific cells that will be efficient at destroying the cancer and improving the patient’s immune repertoire. In addition, they believe that comparing fractal patterns between the donor and the patient can help prevent complications such as transplant rejection and graft versus host disease.

When the researchers analyzed fractal patterns of TCRs from bone marrow donors, they found similar patterns, with a great deal of diversity amongst the TCRs. The donors had similar usage of specific V, D, and J segments in their TCRs as well. The patients who were receiving the bone marrow, however, had significantly less variability in their TCR repertoire. The lack of diversity indicates that fewer damaging antigens, which are produced by infectious agents and caner cells, can be recognized and killed by T cells. By using these fractal patterns, the researchers can find complimentary donors who can contribute to the patient’s repertoire. The researchers hope to optimize the benefits received from a bone marrow stem cell transplant. They add that they believe that the immune system can be improved in the patients. This could help speed recovery after bone marrow transplants.


References:

http://www.sciencedaily.com/releases/201...091849.htm

http://mathworld.wolfram.com/Fractal.html
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Direct Transformation of Adult Stem Cells to Neural Progenitors

May 5, 2013, 1:38 pm
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The use of stem cells for treating injuries and disease has many potential complications. Stem cells, whether embryonic, adult, or induced, could potentially turn into any cell in the body. If this occurs after transplantation into a patient, the consequences could be severe. A central nervous system injury, for example, might end up with muscle cells growing around, reducing the likelihood that the injury could be repaired in the future. In addition, due to their highly proliferative nature, stem cells could potentially cause the development of cancerous tumors.

Stem cells transplants from adult cells have a major advantage over embryonic stem cells. A patient could act as a self donor to procure adult stem cells or induced pluripotent stem cells, thereby negating any possible transplant rejection. Embryonic stem cells cannot be obtained directly from the patient, and could possibly be rejected by the recipient. In addition, preparation of stem cells requires a great deal of work and expertise. Embryonic stem cells must be obtained by the destruction of an embryo, which may be ethically questionable. Adult stem cells are mostly obtained from bone marrow, and produce blood cell precursors. These blood cells are not appropriate for treating many disorders outside of the circulatory system. Induced pluripotent stem cells are derived from normal adult cells, which must be reverted to a more embryonic like state. Once they have been reverted, the cells must then be matured into the desired cell type, and expanded in tissue culture.

Researchers from the University of Wisconsin at Madison recently found a method to directly convert normal adult skin cells from both monkeys and humans into neural progenitor cells, without requiring a pluripotent stem cell intermediate. The neural progenitor cells that were produced are able to mature into a variety of neural cells, and can propagate easily in tissue culture as well as the host. A major advantage to this method is that fewer steps are required to develop the desired cell type. In addition, a patient could donate his or her own cells for the procedure, reducing the risk of transplant rejection. The researchers exposed the adult skin cells in culture to a virus called Sendai virus. Sendai virus is advantageous over other viral vectors used during cell reprogramming, because the genetic information of the virus does not become a permanent part of the cell. This is a safer approach than the use of other viral vectors, which have been linked to tumor formation in previous studies.

After the adult skin cells were treated with virus for twenty four hours, the culture was exposed to moderate heat. The heat was sufficient to kill the virus, but not the cells. This is another advantage to procedure, as no live virus is present when the cells are injected into the patient. The researchers were able to isolate neural progenitor cells, which can further mature and differentiate into nerve cells. The neural progenitor cells proliferate easily in culture as well as in the body. Because they have already begun the process of maturation, there is no risk of the cells turning into different tissue types once injected into a patient. The neural progenitor cells were then injected into newborn mice, and proliferated as normal. There were no apparent defects from the neural progenitor cells, such as tumor formation or the production of unwanted tissues.

Any advances made that help develop cells that can be used to therapeutic purposes are always welcome. However, like many other methods of producing neural cells, this method has some drawbacks. Using a virus to induce cellular reprogramming is always worrisome. The body’s cells have special methods to fight viral infection. Even skin cells can produce an innate response that would decrease cellular replication and turn off certain parts of the cells protein making machinery. This helps prevent the virus from growing in the host. The skin cells are able to produce certain proteins that can cause effects on other nearby cells, and may lead to inflammation. This immune response by the cells may actually prove problematic in large scale production of neural progenitors. In addition, if the virus is not sufficiently killed before the cells have been injected into the patient, this could cause serious consequences. Many patients requiring transplants are given immune-suppressant drugs, leaving them at high risk for complications due to infection. Finding the right balance between destroying the virus without harming the newly developed cells will be important before this treatment can be utilized in humans.


References:

http://www.sciencedaily.com/releases/201...131713.htm
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Cure For Epilepsy Discovered in Mouse Model

May 6, 2013, 7:59 am
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Epilepsy is a group of disorders in which an individual suffers from seizures. The seizures can be mild to severe, and a variety of factors can induce the seizure in the individual. Often times, the cause of the epilepsy is unknown, a condition called idiopathic epilepsy. The seizures are believed to be caused by over active nerve cells within various regions of the brain, although this has not been definitively proven. When the nerve cells become over active, they fire continuously, causing muscle spasms and other symptoms associated with seizures. The seizures can cause injury if the patient falls or is repeatedly hitting a hard surface during the seizure.

Treatments for epilepsy involve administration of anti-seizure medications. However, in some severe cases, the medication is not sufficient to prevent seizures, and more advanced treatments are not yet available. Epileptic seizures can cause significant problems with day to day life. Many patients with severe forms of epilepsy have to limit daily activities in order to prevent accidental injury should a seizure occur. Even everyday activities such as driving can be very dangerous for a patient with epilepsy. Most treatments for epilepsy are preventative and must be taken long-term. A method to stop seizures permanently would significantly enhance quality of life for patients.

Cell therapy is an active area of research for epilepsy treatment. Many research teams have tried implanting inhibitory neural cells into the brain in hopes of stopping the rapid, uncontrolled firing of nerves that causes seizures. However, none of these studies have had successful results until recently. Researchers from the University of California at San Francisco have recently found a way to permanently treat epilepsy in a mouse model of epilepsy. The researchers implanted a specific nerve cell, called medial ganglionic eminence cells, into brains of the mice. Medial ganglionic eminence cells help to inhibit over active nerve signals. The cells were implanted into the hippocampus of the mice, which is a region of the brain associated with seizures. Once implanted into the hippocampus, the medial ganglionic eminence cells were able to permanently stop seizures in the mice. When the medial ganglionic eminence cells were transplanted into other areas of the brain, such as the amygdala, did not stop seizures in the mice.

There are still many caveats and concerns with moving this cell therapy into human patients. Firstly, mouse models of disease are artificially induced by humans. While they can approximate symptoms, and possibly even the cause of disease, the models are still different than the natural disease that occurs in humans. This alone makes it difficult to move potential therapies from mouse to humans. The mouse model of epilepsy was based on a severe, drug-resistant type of human epilepsy called mesial temporal lobe epilepsy. This form of epilepsy usually develops in adolescence, and normally occurs many years after a fever-induced seizure. Normal inhibitory neural cells are often depleted during the course of epilepsy, which may permit over active stimulation of neurons and result in seizures. In mice, the condition is induced using chemicals, which is a very different mechanism than induction by fever. The mouse model does have some similarities to human temporal lobe epilepsy. The seizures are very serious, and the inhibitory nerve cells are deleted as a result of the condition. The time frame is also very different, as mice have a much shorter lifespan than humans. Even though the injection of medial ganglionic eminence cells permanently stopped seizures in the mice, it may not be effective permanently in humans due to the different lifespan of mice and humans.

One of the many difficulties with developing successful cell therapy strategies is finding a method to generate a sufficient quantity of cells to treat patients. Another team of researchers at the University of California San Francisco also found a way to develop cells with similar functions to medial ganglionic eminence cells. When these cells were similarly injected in mice, the seizures were also stopped. However, the cells that are being transplanted into the patient would be donated from another person, or made from stem cells. This increases the likelihood of transplant rejection, which could be particularly problematic with the transfer of cells into the brain. In addition, transplantation of cells that have been developed from stem cells could potentially cause tumors. Stem cell therapy is also in experimental stages, and researchers and clinicians are still trying to determine optimized protocols to prevent such serious side effects.


References:

http://www.sciencedaily.com/releases/201...230317.htm
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Small Molecule Treatment for Muscular Dystrophy

May 6, 2013, 8:53 am
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Myotonic dystrophy is the most common form of muscular dystrophy. It is a chronic, slowly progressing disease that results in muscle wasting, heart defects, and endocrine problems. Myotonic dystrophy is a genetic disorder, passed from parent to offspring in an autosomal dominant manner. An autosome is a normal chromosome in the human cell. A dominant allele, such as the one that causes myotonic dystrophy, only requires one copy to show an effect on the host. An person affected with myotonic dystrophy only needs on mutated copy of the gene to have disease. This also means that half of an affected person’s offspring are likely to inherit the disease from one parent.

The mutation that causes myotonic dystrophy involves an increased number of triplet repeats in a segment of DNA. The mutation involved in myotonic dystrophy causes RNA produced off the DNA to bind to a protein in the cell nucleus, called MBNL1, that is involved in RNA splicing. When RNA splicing is inhibited by the MBNL1 protein being bound, other proteins are not produced in sufficient amounts. This improper protein production results in the symptoms of myotonic dystrophy. There is no cure available for myotonic dystrophy. Treatment involves management of symptoms. Cardiovascular effects are the most important symptoms to treat, as they are responsible for the majority of deaths due to myotonic dystrophy.

Researchers from the University of Illinois recently developed a small molecule that is able to enter the cell nucleus and disrupt RNA binding to the MBNL1 protein. By breaking up this binding, MBNL1 protein is able to function normally and assist with alternative splicing of RNA. Normal levels of other proteins can then be produced in the cell. The molecule, which has not yet been named, is water-soluble, which allows it to easily enter the cell and nucleus. It is specific to the repetitive RNA sequence associated with myotonic dystrophy, so it would not bind to other RNA molecules and affect normal cellular functions. The researchers found that the molecule was able to break up the protein-RNA interactions in live cells, the first such study to show a molecule capable of this function. The researchers were able to view the clusters of RNA and MBNL1 protein breaking up with microscopy, and also measured increased MBNL1 protein activity in the cells after treatment. Amazingly, this began to occur within only a few hours after treatment, indicating a very rapid effect.

The next steps in studying this molecule would be fruit fly and mouse studies. Seeing the positive effect in living cells is an important start, but tissue culture cells do not accurately depict what happens in the entire body. Other cellular factors within the body may affect how the molecule is distributed and taken up by the cells. The route of administration must also be determined in an animal model. The molecule must be able to enter a large variety of cell types in order to be effective throughout the body. Certain routes of administration may result in the molecule being degraded by the host. The dosing must be studied to make sure enough of the molecule is available to the body’s cells, without causing negative reactions. The number and timing of dosages must also be determined in animal studies, as the cell studies did not indicate how long the molecule is able to function in vivo. Modifications may be needed to the molecule to help aid in proper distribution throughout the body. In addition, cell culture studies may not adequately demonstrate potential toxic effects of the molecule.

Indeed, moving from tissue culture studies of cells to human clinical trials is a long, arduous process. There are many factors that need to be determined before human studies can even be considered. As exciting as it is that a potential treatment of myotonic dystrophy may be available, there are still many years until the therapy could be available for human studies. However, finding a molecule that can directly stop the RNA-protein clusters that seem to cause myotonic dystrophy is an important first step. Even if the molecule being studied is not ultimately usable as a treatment for myotonic dystrophy, it can help future research leading to the development of a successful treatment, or even cure, for myotonic dystrophy.


References:

http://www.sciencedaily.com/releases/201...145107.htm

http://en.wikipedia.org/wiki/Myotonic_dystrophy
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Lowering Costs for Genome Assembly

May 6, 2013, 10:49 am
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The time requirement and cost of sequencing genomes has decreased exponentially in recent years. The human genome project, in which the entire human genome was sequenced, took 13 years and three billion dollars. Now, an entire human genome can be sequenced within a few days. While human genome sequencing is viewed as a way to provide individualized medicine and screen individuals for susceptibility to certain genetic conditions, sequencing the genomes of other organisms is viewed as a way to gain information about different species. Genome sequencing is becoming an important tool in scientific research, to help identify species and find important DNA sequences and proteins. Genome sequencing helps researchers group together similar organisms to find both beneficial as well as detrimental properties of the organisms. Many organisms have had their genomes sequenced, including humans, monkeys, apes, plants, mice, and a myriad of bacteria, to name just a few. By sequencing the genomes of so many different organisms, researchers can determine evolutionary relationships between different species, important genes for pathogenesis in disease causing microbes, and proteins that can be utilized for human benefit from plants, fungi, and bacteria.

The Department of Energy Joint Genome Institute is interested in sequencing microbial genomes in order to determine which microbes might be useful for production of biological energy sources. They are studying microbes that could potentially have effects on carbon processing, energy production, and environmental concerns. In fact, the DOE Joint Genome Institute is currently involved with or funding approximately twenty percent of the whole genome sequencing studies that are underway around the world. The potential benefits of microbes for solving environmental issues are numerous, and could help researchers at the DOE Joint Genome Institute find methods to curb the production of greenhouse gases and other pollutants.

Whole genome sequencing usually is done using what is called the “shotgun method”, which involves sequencing many tiny, overlapping fragments of DNA, then putting the pieces together in the correct order. While the sequencing itself is relatively easy and straightforward, putting the segments back together can be more difficult. The small fragments are ordered by using overlaps that occur within the sequences, which is a very time consuming process. The current preferred method for genome sequencing is called the Sanger method. Using the Sanger method, nucleotide sequences of less than a thousand bases are sequenced and then ordered together. This requires the production of multiple libraries of the genome, in order to get sufficient overlap of the nucleotides to aid in restructuring.

Along with Pacific Biosciences and the University of Washington, the DOE Joint Genome Institute worked to develop a more efficient, fully automated system to help put the segments back together in the correct order. By making the process of restructuring the genome faster and more efficient, the cost of reconstructing genomes will also decrease rapidly.

The technique for genome assembly is called the hierarchical genome assembly process. The technique uses a single molecule, real time DNA sequencing system, which is a system developed by Pacific Biosciences. This allows the sequencing of long pieces of DNA, up to tens of thousands of nucleotides long. A single library of nucleotide sequences is produced, composed of these very large fragments of DNA. The longer stretches of nucleotides being sequenced and the reduction from multiple genomic libraries to only one library means that there are fewer nucleotide sequences to combine together, which makes the genome restructuring process faster.

To test the hierarchical genome assembly process technique, the genomes from three separate microbes were sequenced. All of these microbes had previously had their genomes sequenced by the DOE Joint Genome Institute using conventional methods. The sequences obtained using the hierarchical genome assembly process techniqure were then compared to previously obtained data. The sequences matched up, indicating that the hierarchical genome assembly process is accurate as well as fast. The next step that the researchers at Pacific Bioscienecs plan to take is expanding the ability of the hierarchical genome assembly process to help reconstruct and sequence genomes from larger, more complex organisms. Improvements in genome sequencing such as those provided by the hierarchical genome assembly process will help make whole genome sequencing an even more accessible and important tool for many areas of biological research.


References:

http://www.sciencedaily.com/releases/201...145933.htm
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Evolution of Microscopy

May 6, 2013, 1:41 pm
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The field of Biology owes a lot to Microscopes. It was the invention of this very instrument, which widened the horizons of Life Sciences. From the physical world of plants and animals, the focus was drastically shifted to the world beyond the sight of naked eyes--the Microbiological World (the world of bacteria, fungi, protozoa, algae and though acelular, viruses too!). Here in this article, I would take you through the evolution of microscopy, encompassing the times of single eye lens to the modern day Electron and UV Microscopes!

How it started:
Anton van Leeuwenhoek, one of the most revered scientists in the history of Biology, was the one who did the astonishing invention of world's first "Microscope" between 1670-1700, turning him from an ordinary draper to a pioneer in Biology. Though, his contemporaries as well as the primitives, had tried their hands on making a magnifying lens combination (use of single eye magnifying glass dates back to 13th century; Jansen in 1590, was the first to use a combination of lenses in a tube to get a 10X magnification) Anton's lens tube (holded single lens) was so craftly designed that it gave him a magnification of 270X, outdoing the work of everyone else! Following is the actual sketch and image of Anton van Leeuwenhoek's work:
[Image: Van_Leeuwenhoek%27s_microscopes_by_Henry_Baker.jpg] [Image: 144px-Leeuwenhoek_Microscope.png]
[Note: Images are free to use/share even commercially)
The needle in front of the orifice(holding the finely grinded lens) was used to place the objects. The position of the needle could be finely adjusted to get magnification of desired levels!

It is with this particular work that Leeuwenhoek entered the field of Microbiology. He was the first person to observe motile sperms, bacteria, fungi, microbial flora and fauna of aquatic life and turned his observations into sketches giving him the dignity he still holds today (The Father of Microbiology)!

Invention of Achromatic Lenses: Emergence of Compound Microscopes:
Chester Moore Hall, another non-scientific background turned scientist! He was a lawyer by profession and led to the highly significant invention of achromatic lenses in 1729. Chromatic and spherical aberration of lenses was a big hurdle for coupling two or more lenses together to increase the magnifying power. These effects lead to focusing of lights of different colors in different planes when passed through an ordinary lens. So, whereas a single lens could give a good view of magnification, coupling the lenses would amplify the problem of aberrations, leading to a completely out of focus image.
. Hall's discovery changed the entire prospect of Microscopy and Telescopy, paving the way for compound microscopes and telescopes.
[Image: Chromatic_aberration.png] [Image: Lens6b.png]
First image shows the problem of chromatic aberration in ordinary lens, second image shows the correction through achromatic lens(doublet).
(Images free for reuse)

Birth of Compound Microscopes:
With the widespread realization of characteristics of Achromatic lenses, numerous companies producing Microscopes, started working on making a better version of Microscope, which led to the emergence of Simple Compound Microscopes. (Precise details of who first came up with compound microscope with achromatic lenses aren't available, though Italy is considered the most prolific producer of high end microscopes at those times ie late 18th century)
The compound microscope basically came-up with Achromatic objective and eye piece in the same tube.

Development on Light Source
After the invention of achromatic lenses, the next hurdle was in the use of a light source for illuminating the sample. Earlier version used Critical Illumination, which led to appearance of the light source's image in the final focus (termed Filament Glare/image), apart from the problem of non-uniform illumination of the sample. With the advent of Kohler Illumination (1893), the problem of glare and non-uniformity was well dealt with. Kohler used a set-up in the microscope, involving a Collector Lens, Collector Diaphragm, Condenser Diaphragm and Condenser Lens as a way to make sure that specimen is illuminated uniformily and no glare appears in final image.
This was a major development, and still used today.

Emergence of Fluorescence Microscopy
Fluorescence microscopy added another dimension to the visualization of specimens in a more clear way (as the specimens themselves act as the source of light!). In most simple terms, it involves the labeling of the samples with flourophores, which are excited upon bombarding photons. The fluorescent light is separated from reflected light using filters, and used to create an image of the specimen.
Oskar Heimstädt, a physicist, was the inventor of Fluorescent Microscope, in 1911.

The Limitation of Light Microscopes: Emergence of Electron & UV Microscopes:
A big limitation of Light Microscopes was the size of objects it could magnify. If somebody needed to focus on objects smaller than 350nm, the light microscope could never do it! So, basically, going inside the details of the cells was only an imagination till the advent of next generation microscopes-Electron & UV Microscopes. The very basic reason that light microscopes cannot focus on objects less than 350nm in size is that: "Size range of the object that can be focused by the microscope, depends upon the wavelength range of the source of light being used!" So, visible light cannot be the source of illumination, if target object is smaller than light's own wavelength i.e 350nm. This is where the need for better source of illumination was felt, and that led to the idea of using a beam of electrons or UV light to solve the purpose.
Knoll & Ruska are coined the fathers of electron microscopy (1931). An electron microscope can visualize objects as small as 50 picometer! (almost 100000 times shorter than that by light).

There after, many sources of illumination have been tried ranging from X-ray to laser light to infra-red radiations. All with the purpose of focusing the object of different sizes.

Apart from that, little and progressive developments were made in the way of processing the light reflected by the specimens, leading to variety of methodologies like Phase Contrast, Bright Field, Dark Field, Confocal microscopy etc.

Literature is in abundance, this was just an attempt to make you familiar with the series of events that led to the current era of Microscopy.

Suggested Readings:
http://cbe.ivic.ve/mic250/pdf/microscope.PDF

http://www.celestron.com/c3/images/files...esinfo.pdf

http://micro.magnet.fsu.edu/primer/pdfs/...beyond.pdf

Happy Reading!

Thanks
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Stem Cell Niche

May 7, 2013, 3:01 pm
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Stem cells with tumor cells are the only cells in human body that are able to proliferate and differentiate indefinitely. Self renewal is the key process in human organism because it has great importance in tissue homeostasis and regeneration. Surely, the promise of stem cells biology has given a hope for treatment of many diseases in regenerative medicine.
Homeostasis of human body is maintained by continuous stem cells division. By self-division and differentiation of daughter cells, stem cells are responsible for replacing of short-living and highly differentiated cells in skin, testicles and blood. Of course, this process must be strictly observed, because it can cause many dysfunctions in our body. Because of their importance, stem cells should be preserved as much as possible from damage or loss.

If little amount of cells differentiate, big number of cells can be created and it can lead to secondary mutation and tumor genesis. On the other way, if big amount of cells differentiate, the stem cell population may be reduced. However, critical decision between stem cell self-renewal and differentiation is controlled by microenvironment in which stem cells are located called stem cell niche. Stem cell niches provide support for stem cells and signalization (hormonal, neural and metabolic). Niches have been found in peripheral nervous system, skin, hair follicle, prostate, blood, breast, bone marrow and intestines. Many recent studies have begun to reveal different critical components of many stem cell niches. These critical components include various cell types like inflammatory, mesenchymal, glial, vascular and neuronal, then other factors like oxygen tension, temperature and matrix rigidity.

Interactions in the stem cell niche

There are several interactions in stem cell niche. Cell- cell interactions provide structural support, produce soluble signals that control function of the stem cell and have role in adhesion. Extra cellular matrix also has interactions with stem cells, and their interaction provides mechanical signals which allow stem cells to have adequate response to physical forces from the outside. Also, temperature, chemical signals and shear forces which are provided by the stem cell niche influence stem cell behavior.

Signaling pathways

Gene activated cascade of events dictate stem cell fate and function. These signaling pathways include Notch, Sonic Hedgehog, Wnt genes and BMI-1. Role of the Notch is very important in many stem cell niches, mainly in muscles, gut, mammary gland and hematopoietic system. This signaling pathway has role in stem cell division and it is activated when ligand and Notch receptor make connection. The Wnt genes has still blur image of their function, but they may have role in direct induction of stem cell self- renewal process, and possibly, they can influence stem cells in the niche. The BMI-1 signaling pathway has been found in neuronal stem cells and hematopoietic stem cells. The most possible function of BMI-1 signaling pathway is other somatic stem cells regulation of self- renewal. Sonic hedgehog signaling controls many growth aspects, and as many studies have shown, this signaling pathway controls stem cell- like cells in neocortex and proliferation of the cells in hippocampus and ventral forebrain.

Cell differentiation in stem cell niche

In stem cell niche, when stem cells receive signal, they begin division. This division can be asymmetric, bigger part stays in niche as stem cell, and another becomes a progenitor cell, leaves stem cell niche and continues differentiation. Also, division can be symmetric, and in this division type, both stem cells remain in niche. The key role of stem cell niche is adequate signaling system, which can tell stem cells to divide or not to divide. If niche doesn’t provide appropriate signal, stem cells begin to differentiate in short amount of time. Progenitor stem cells move away from the niche, and they are escorted by guardian cells.

If cell differentiation prevailed, the stem cell population within a niche would be decreased, and if self- renewal continued uncontrolled, the result would be quick tumor development. The role of niche is obvious, because niche provides necessary balance between differentiation and division. The niche environment is responsible for inhibition or induction of stem cell differentiation or division, based on the composition and size of stem cell niche. Surrounding tissue and extracellular matrix signals provide cell identity and commands their behavior. Functional cells arising from stem cells differentiate in intermediate- differentiated progenitor cells, that after a several divisions and differentiations, become differentiated cell, without ability to proliferate and that cell is treated as finally differentiated.

In every tissue, stem cells have high capacity for proliferation, but not every human stem cell divides with high frequency. Researchers have proven this by using fluorescent labeling to mark skin stem cells. These skin stem cells within the stem cell niche began to divide rapidly.
Stem cells have enormous potential in regenerative medicine in repairing diseased or damaged tissue because of their tumor initiation role. The stem cells niche have potential role in cancer treatment. These niches are maybe potential targets for radiation and chemotherapy treatments in order to destroy tumor stem cells. For example, mammary gland stem cells are controlled by reproductive organs as well as the niche to produce new tissues in order to create more complex way of stem cell self- renewal as well as chance for tumor progression. Similar to this is prostate tumor treatment. In prostate tumor, stem cell niche is in the basal layer, proximal to urethra, and this region has been identified as stem cell niche in the prostate gland.

Conclusion

Stem cells are fantastic and promising solution for regenerative medicine, but these cells are not only important in tissue renewal. As these cells must react very fast, they receive input information from their niche, which directs their destiny. When we understand complete interaction between stem cells and niche, we will dictate their activities to promote tissue regeneration. On the other hand, targeting these niches can help us in battle against many diseases such as tumors.
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Status of Biotechnology in South Africa

May 8, 2013, 5:09 am
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South Africa is one of the African countries that have embraced biotechnology. In the continent of Africa, the Republic of South Africa is the most southern one. Botswana, Mozambique, Namibia, Swaziland and Mozambique are the immediate neighbors surrounding South Africa.

[Image: sf-map.gif]

During the apartheid regime, South Africa found itself in isolation from the rest of the global community. However, she has made huge strides in the development of health and agricultural biotechnology. Today, she is one of the leading sub-Saharan countries that have domesticated biotechnology both in Agriculture and health sectors and is an exporter of biotechnology products.

In the health sector, South Africa has moved with speed to address HIV-AIDS menace by leading the way in finding solutions to this public health. Currently, at the University of Cape Town, there are six potential novel candidate vaccines that are under evaluation. In the late 2003, she did two phase 1 trials for the vaccines, emerging the first African country to carry out multiple HIV-AIDS vaccine trials. Additionally, she was the first country to do trials on preventive vaccine against HIV-1 C subtype3 in partnership with international public-private partnership (PPP), the national institute for communicable diseases and the medical research council (MRC). To enhance this, the government of the republic of South Africa has cultivated public-private partnership between domestic and international players that has heavily supported work on Tuberculosis, malaria, HIV-AIDS. Additionally, she has created three biotechnology innovation centers that act as the nuclei platform for all biotechnology related concerns. These centers are; the East Coast Biotechnology Consortium (EcoBio), Cape Biotechnology Initiative and Biopad in Johannesburg. In South Africa, biotechnology tools used in agriculture include; molecular diagnostics, tissue culture, marker assisted selection, molecular characterization and genetic modifications. Most of the sub Saharan African countries have developed and domesticated the use of tissue culture in the development of crops that are of high quality, disease and pest resistant, drought resistant and early maturity. However, the application of genetically modified crops using genetic modification technology is limited to some countries including South Africa. The genetically modified crops commercially produced in South Africa are cotton, maize and soybean.

In animal agriculture, major biotechnology-based research programs have been put in place to promote production and good health. For example, there has been identification, cloning and expression of genes together with preparation of prototype viral-vectored and genetic vaccines for bovine ephemeral fever, African horse sickness, rift valley fever, Newcastle disease and lumpy skin fever. This has seen veterinary sector flourish in this African country. This research is mainly carried out by Onderstepoort Veterinary Institute (ARC-OVI), a flagship institution of the Agricultural Research Council.

Crops such as melon, tomato and potato have undergone in-house genetic transformations. There have been genetic transformations of three potato cultivars that confer resistance to potato virus Y and potato leaf-roll virus. Additionally, there has been a gene transfer system for flowering bulbs of indigenous origin. This has been achieved by ARC-Roodeplaat Biotechnology Division.

Biotechnology measures have been incorporated in the production of guava, papaya, pineapple, ginger, avocado and coffee through tissue culture techniques in breeding programs. This is developed by ARC - Institute for Tropical and Sub-
Tropical Crops.

South African institutions have come up with embryo rescue techniques in order to create inter-specific crosses in dry beans and also facilitate sunflower breeding. They have developed techniques in plant regeneration from cells and tissues in order to create transgenic plants through ballistic bombardment in groundnuts. The use of marker assisted selection for nematode resistance in soybean has also been domesticated. Additionally, in the quest to produce disease free dry been seeds, meristem culture techniques have been introduced and are on advanced research levels. South Africa has seen the incorporation of foreign genes in the enhancement of herbicide resistance in lupins and drought resistance in the highly planted groundnuts, DNA level cultivar identification in soybean, sunflowers and groundnuts. Nevertheless, there has been breeding of maize cultivars that are disease resistant to ear rot and maize streak diseases. All this has been done by ARC- Grain Crops Research Institute.

There is a major development in successfully transforming and regenerating of a maize (strain HI-II), a laboratory strain of maize through genetic engineering of cereals, enhancement of protein quality of sorghum through genetic modifications and genetic enhancement of maize in order to promote food safety. Maize safety has been enhanced through the introduction of four plant anti-fungal genes that combat contamination by Fusarium moniliform, a post harvest pathogen, which produces mycotoxin, toxic to animals and human beings. This research was done by CSIR (Foodtek /Bio-chemtek).

The university of Stellenbosch (institute of wine biotechnology and institute of plant biotechnology) established an efficient regeneration and transformation systems for grapevine, and the construction of genomic and cDNA libraries for grapevine cultivars. Also, they have identified grave cultivars using genetic marker technology, cloned and characterized PGIP encoding gene in grapevine. This research institute has also come up with characterization and genetic manipulation of carbon flow in grapes and sugarcane crops. This has helped the alcohol and wine production industries produce new and desired type of brands for consumption. However, health concerns are the emerging developments in this field.

Micro-propagation techniques of indigenous trees, for example, marula and development of vaccines for diseases in the poultry industry has been achieved through research done by the University of the North and the University of the Free State respectively. The University of Cape Town in collaboration with PANNAR has developed reliable techniques for regeneration and transformation of local maize varieties, engineered transgenic resistant maize crops against maize streak virus and also has probed the tolerance of plants to desiccation.

Having said these advances in biotechnology, this African state has faced challenges in the implementation of policies to support full domestication of the discoveries. There is also lack of human resources in terms of researchers and R&D personnel due to brain drain and disparities in educational institutions based on race. There is also a relatively limited level of venture capital investment in Research and Development in health biotechnology.
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Emerging Era of Bio-Nano-Robots

May 8, 2013, 12:33 pm
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THE TRIGGER
In 2005, researchers from the Rice University came up with an extra-ordinary research. It was about a successful test of a "Four Wheeled" molecule, driven on a nano-scale gold surface, what you may understand as "A molecular car driven on the road of gold!" The wheels of the miniature car were made of Bucky balls (buckminster fullerenes or C60-80 molecule), with a body/chassis and axle synthesized by palladium-catalyzed reaction(s).
Flat gold surface ensured an inert road for the nano-car, on which it could move translation-ally without tumbling on it's wheels. Steering of the car could be controlled by using Scanning Tunneling Microscope tips which can induce a change in electric potential between the surface and the molecular car, leading to motion of the molecule!.
There are other modes of inducing the motion too, like application of heat energy to induce vibrations in the surface to cause the movement of the molecule (the conventional means of powering the nano-scale motors). Following video helps explain the concept of fueling of nano-motors:




Development of such a molecular motor with wheels and chassis, resembling a macro-world truck/car was an altogether new approach towards making nano-motors. Also, Tufts University Scientists has reported a single molecule nano-scale motor that could rotate at a point upon empowering with Heat/STM tip. Their molecular motor basically had a thioether molecule with 2 carbon chains around. But, Rice University's model is truly a molecule scale car, and indeed the future of Nano-robot designs. If such motors/molecular cars could be developed for practically any surface, it might lead to a radical rise in the prospects of nano-medicine delivery and nano-bot (nano robots) mediated tissue repair. Thus the research acted as the stepping stone and an advanced reminder for further research on molecular motors that could lead to a bio-compatible Nano-Robot!

BIOTECHNOLOGICAL LEAPS IN NANO-ROBOTS' DEVELOPMENT
Considering the need for a bio-compatible, yet controllable molecular motors, biotechnology came up with the ideas of using some non-pathogenic naturally occurring molecular motors (some in the form of whole bacteria, some as flagellar motors, other as artificial magnetotactism) as the immediate and efficient solution to creating a versatile and robust Nano-Motor/Bio-molecular Car, which could carry the payload and deliver it to the site concerned and even carry out the tissue repairs of injured sites.

Bacteria as Nano-Robots
Non-pathogenic forms of flagellated bacteria were the first hopes of the scientists as a naturally available fully functional molecular robot. The movement of such bacteria according to changing concentration of salts/pH/nutrients (called as Chemotactism), has been seen as the best way of controlling the motion of these Biomolecular-Robots. But recently, with the reports publishing on the application of Flagellated MTBs (Magnetotactic bacteria) as the fully controllable way of delivering payload to even deep blood vessels at specific points, the interest has shifted to Magnetotactic bacteria as future Bio-Nano-Robots, than the chemotactic bacteria.
Following is a link to freely available research article on MTBs as Bio-Robots:

http://wiki.polymtl.ca/nano/images/1/10/C-2008-MTB-BioRob-Sylvain.pdf

Bacterial Flagella as a Nano-Motor
The mode of functioning of bacterial flagellar apparatus makes it a potential candidate for being used as a motor to drive molecular chassis made of synthetic materials. Basically, bacterial flagella works on the principle of electrochemical potential generated by differential concentration(s) of H+ ions (see video below). The functioning is quite similar to artificially induced potential by STM Tips, but unlike STM tips (which is an external inervention), flagellar motor has an inherent mechanism to generate the potential using it's own apparatus. So, an extraction and fitiing of this apparatus in synthetic chassis, could rather enable functioning of the molecular cars in biological fluids too, where flagellar apparatus has the tendency to function.




Induced Magnetotactism: Biological way of converting normal bacteria to Magnetotactic Robots

Recently (September 2011), scientists from Department of Mechanical Engineering & Mechanics, Drexel University, Philadelphia, USA and
Department of Aerospace Information Engineering, Konkuk University, Seoul, South Korea came up with a new way of "Inducing" magnetotactism in otherwise normal bacteria! They converted Tetrahymena pyriformis GL , a normal flagellated bacteria, to a magnetotactic bacteria by inserting iron-oxide nano-particles into the same. The resultant bacteria could extra-ordinarily be controlled very efficiently by using time varying magnetic fields!
. This really paves the way for making any flagellated non-pathogenic bacteria, a cellular robot, which could be used for delivery and manipulation at specific sites in the body, just by driving it with a magnetic field!

The above listed instances of Biotechnological approaches to Nano-Robots' development really make us realize the huge potential & applications of the living world for the new age discoveries, even as sophisticated as Nanotechnology. There's a lot of untapped potential in the simple living systems like bacteria. Biotechnology has made the task of making a nano-robot extremely simple, which was otherwise regarded as extremely daunting by world renowned Physicists, Mechanical engineers, mathematicians etc.
The field of biotechnology might currently seem extremely limited to the new entrants, but may be it's because of the fact that what we see as "all the doors already opened", could just be the windows only! Doors are yet to be opened, and for that one needs to believe, think and act in biotechnical way for every possible problem being faced today!

"Solutions to the problems of living/natural systems cannot be synthetic, it has to be living/natural only!"


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Quorum sensing in Bioreactor Operation(s)

May 8, 2013, 2:45 pm
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Introduction:
In most simple terms, Quorum Sensing refers to change in gene-expression in response to change in the cell density/cell population. It's exhibited only by those bacteria, which have the capability to release special signal molecules called auto-inducers, whose concentration is directly proportional to the cell density. For, the cells to become physiologically active and divide, they need to sense a minimum threshold of the auto-inducer, in absence of which, cells donot divide, and remain in the phase of lag/slow growth and eventually die.
In gram-positive bacteria, forms of oligo-peptides are used as auto-inducers, while gram-negative bacteria use acylated homoserine lactones as auto-inducers.

Role in Bioreactor Operation(s)
Deciding factor for Inoculum Density
Refer any literature on bacterial biomass production in bioreactors, and you'll observe that a fixed volume of reactor operation needs an optimal concentration of inoculum biomass to initiate the run. Where as higher concentrations can work, any concentration of biomass below a fixed value won't be able to successfully inoculate the bioreactor. This is a direct consequence of QS. Auto-inducers are the signal molecules that synchronize the physiological activity of the bacteria and enable them to express the house keeping genes, including those responsible for the synthesis of auto-inducer. But any bacterium never senses it's own auto-inducer, and always need an alien auto-inducer (synthesized by other cell) to activate the genes. When, the concentration of cells in the inoculum is very less, then upon transferring it into bulk volume of the reactor, diffusion limitations unable the interaction of auto-inducer with the complementary receptors on bacterial cells. But when the concentration is high, every cell can detect auto-inducer of each other's cell, further amplifying the expression of more auto-inducer synthesizing genes. This synchronization leads to a loop of auto-inducer synthesis and high expression of house keeping genes, leading to fast multiplication of the cells.

For Enhanced Biofouling of Membrane Biorecators in Waste Water Treatment
Waste water treatment is done normally by using Membrane Bioreactors, in which biofilms of bacterial cells are grown on reactor membranes, which degrade the toxic wastes of the water to be treated. And, to increase the cell density in the biofilms, synthetic analogs of auto-inducers are supplied, which trigger the growth and multiplication of the bacterial community responsible for the density of biofilm. A recent report on biofouling control in membrane reactors has proved that if the inhibitor(Porcine kidney acylase I) of N-acyl homoserine lactone (AHL) auto-inducer is applied to the culture, it prevented the biofouling of the membranes, thus establishing the quenching effect on auto-inducers and hence the dependency of biofouling on auto-inducers.

Bioreactor Clean-up in Industrial Set-up
Biofilming of contaminating microbes in the pipes and orifices of bioreactors in industrial set-ups is very common. And, considering the fact that Biofilms are highly toxic and tolerant to most antimicrobials, their clean-up is very difficult. QS quenching by the use of inhibitors, comes handy under such circumstances to clean-up the biofilms growing in sensitive locations in industrial fermenters.

Wall effect
It's very common to have observed the growth of bacterial culture (being cultivated in bioreactor vessel), on the walls of the reactor. It leads to very high consumption of nutrients by the wall attached bacterial growth, but no effective increase in the biomass grown in the reactor (which is sampled regularly). This effect is called as wall effect and is a direct consequence of high QS among the wall attached cells which tend to form a biofilm/aggregate there through concerted activity induced by auto-inducers.


Spent Media Induced Activity
It has been observed by many scientific groups, that supply of spent media to the batch reactors elicits the growth and productivity. And, it was quite evident and has been proved that the elicitation is actually an effect of auto-inducers present in the spent media, which were synthesized by the cells growing in that media. It's thus a novel and cost effective way of eliciting the response of cells towards growth and productivity.

It's thus evident that, QS plays a significant role in successful operation (and even maintenance) of bioreactors. Many scientific groups tend to forget the involvement of auto-inducers in routine cultivation of cells in bioreactors, which if realized can significantly enhance growth & productivity through as simple measure as using the spent media as elicitor! I hope this article added/updated your knowledge about QS!

Following is a simple animated depiction of QS:



Thanks!
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The Green Revolution in Sub-Saharan Africa

May 9, 2013, 7:27 am
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The term green revolution refers to all the technological developments that happened in the field of agriculture in the 1960s. This revolution started during the neo-colonial era when agriculture was viewed as a commercial activity rather than a subsistence activity led Norman Borlaug-a green revolution father. Green revolution started with a single private-public experiment with the Mexican wheat. Although the term Green Revolution initially meant development in wheat and rice, high yielding varieties have since then been incorporated in the system. These crops include major crops in developing countries such as sorghum, cassava, millet, maize, beans and millet. However, this historic transformation of traditional farming methods was not universal as it did not continue in Africa at that time.

[Image: 5559634670_0f7bf718fd.jpg]

Sub Saharan Africa contains sixteen countries of the eighteen most undernourished countries worldwide. This is because that region registers a continually worsening per-capita production of food yearly. This is happening despite having the largest population predominantly practicing small scale farming, being the most hunger and poverty stricken region and being the continent that receives the most attention from the international community.

In low-income regions elsewhere in the world like Colombia and Asia , the introduction of fertilizer, high-yield seeds and small-scale irrigation that began in the mid-1960s boosted food productivity and opened the escape route from extreme poverty for huge populations. This agricultural takeoff in sub-Saharan is an urgent need and a possibility. This part of Africa faces a myriad of challenges that can only be resolved by introduction of new methods that can revamp agricultural production so as to enable the region cater for its immensely growing population. Sub-Saharan Africa experiences perennial droughts, animal and plant diseases, environmental degradation and climatic change, depletion on soil nutrients, soaring world food prices, political instabilities, pestilence and lack of personnel to help in revamping this important sector in the economy.

In this 21st century, The Rockefeller Foundation started a six-year program on improved crop varieties in Africa. This was based on specific pillars that have seen a major advancement in food security especially in East and South African countries. Cultivation of local talent in plant science, scientific development of more productive fertilizers and crops, modern farming methods, appropriate agricultural policies and getting government’ commitment on agriculture, creating conducive agricultural environments and irrigation were the main structures that were put in place to ensure the six-year plan was a success.

Through African agricultural research institutions, the idea of green revolution has been greatly boosted in the advancement of Norman Borlaug’s idea. Through institutions like the Alliance for a Green Revolution in Africa (AGRA) funded by the Bill & Melinda Gate Foundation, the Rockeffeler Foundation and other government sponsored institutions and universities, having African scientists have rolled their sleeves in the quest of this achievement.

Among the major achievements attained by this program, it has supported the development and release of more than one hundred new crop varieties, dozens of which is a breeding of a breakthrough rice variety that is proved equal to the challenges facing other rice farmers in Africa such as weeds, pests, weeds, drought and diseases that have hindered the rice farming for decades. Since the 1990s, new varieties have been developed including the New Rice for Africa or Nerica among others that are now been cultivated on more than 350 000 acres in the sub-Saharan African countries. These crop varieties have proved successful and sustainable in this hostile African environment.



Nerica, besides its advantages in food supply and source of income, it has far-reaching social effects. It has a short growth cycle, weed, disease and pest resistant. However, the Nerica program has been beset by problems getting the rice into the hands of farmers, and to date the only success has been in Guinea where it currently accounts for 16% of rice cultivation

The introduction of the Green revolution in Africa has however faced challenges that have seen it less successful. Some of the major reasons stated as hindering the revolution include insecurity, widespread corruption, and lack of proper infrastructure, land partitioning, lack of knowledge and general lack of political good will from African governments to appreciate and incorporate agricultural biotechnology in their farming habits. Poor infrastructure has posed a challenge in that farmers in the remote areas can no longer access modern and high-yielding farm inputs that are resistant to the hostile environmental conditions. In Africa, there is a more diverse range of suitable crops that fits the climate and soils. This makes engineering of farm inputs difficult. Yet it is possible to develop these higher-yielding crops suitable to Africa’s diverse regions, especially if the region’s farmers become part of the breeding, testing and selection processes in the production path.

Additionally, Africa has fewer teams of trained scientist that are available to put the knowledge into practice for the purposes of large breeding programs. Division of land into small pieces has also hindered the progress of the revolution. These farms favor small scale farming instead of commercial farming.

To achieve their objectives, these foundations have given in to the need of developing genetically engineered seeds and recruitment and training of local African scientists familiar with circumstances on particular areas where they work so as to practice crop-breeding programs. The Rockeffeler foundation is currently supporting 25 crop breeding teams in various agricultural research institutes as well as training 35 to 40 masters’ students and 50 plant breeding doctoral students from Africa in different learning and research institutions in the world. The founders of this foundation, however, recognize that for a full-scale Green Revolution in Africa, there is need to educate more talent so as to multiply the number of output to the desired level.
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Basics and Developments in Microbial Fuel Cells (MFCs)

May 9, 2013, 3:03 pm
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Microbial Fuel Cells or in technical words, Bio-electrochemical cells, are the bio-technical analogs of conventional Electrochemical cells. Where as an electrochemical cell converts the energy derived from chemical reaction(s) into electricity, an MFC utilizes the energy derived from biochemical reactions taking place inside the microbes, for converting into electricity.

Let's understand the concept very briefly:
1. Electrochemical cell has two half cells-Anode half and cathode half.
2. Both cells are connected to each other through internal perforated bridge (for ions to flow between the cells) and external wires connecting the electrodes of two cells. This completes the circuit.
3. Chemicals are used as electrolytes. Reaction of electrolyte in anode half creates an excess of electrons which are transferred to the cathode half, where reaction creates deficiency of electron.
4. Electrons thus travel and lead to electricity generation. Following image could help in understanding the concept:
[Image: Untitled.jpg]

A Microbial Fuel Cell has minor differences. It's anode half has microbial culture (anaerobic condition preferred) instead of electrolyte. Microbes are allowed to grow there. Cathode half is filled with a salt solution (often NaCl) in oxygen excess conditions. Electrodes are of carbon in both cells, usually. When cells grow, their metabolic electrons (viz. from Electron Transport Chain (ETC)) are transferred to Anode half, which get transferred to cathode half to induce H2O production by reaction between H+ and O2. The flow of metabolic electrons through wires thus produces electricity. Please refer image below:

[Image: Untitled2.jpg]

The electricity generated is very low, but competent enough to replace the now common electrocemical batteries.

Developments:

a. Electron Transfer From Bacteria to Anodic Electrode
In the earliest form of MFCs, mediators were used to mediate the transfer of metabolic electrons from bacteria to the electrode. The mediators were REDOX mediators, so that they penetrated the cells in oxidized form and get themselves reduced by the metabolic electrons. The reduced mediator also being permeable through cell membrane, like oxidised mediator, would reach the anode to get oxidized, transferring electrons in the process. The process would keep repeating, generating electricity. Examples of such mediators are: methylene blue (MB), thionine (Th), meldola's blue (MelB), anthraquinone-2,6-disulfonate (AQDS), potassium ferrocyanade etc

Discovery of certain species of bacteria which could directly transfer the electrons to the anode without the need of mediators really revolutionized the idea of making MFCs. Such MFCs were called Mediator Less, and have become a trend among the high school students for science fairs, owing to the ease of developing it.
Examples of such species are: Shewanella putrefaciens, Geobacter metallireducens, Aeromonas hydrophila etc

b. Carbon Cloth & Carbon Nanotubes for Electrodes
Considering the fact that amount of electricity produced is not only limited by the density of bacterial culture ans efficiency of transfer, but also by the surface area available for electron transfer, several scientific groups have tried to use Carbon cloth as an alternative to normal carbon electrodes (Carbon cloth is basically as sheet of carbon). Recently in 2011, a scientific group from the esteemed University of Hawaii, University of Southern California, University of New Mexico, and Saint Louis University (all in United States) published a research on the "Fabrication of macroporous chitosan scaffolds doped with carbon nanotubes and their characterization in microbial fuel cell operation!
Whereas, the microporous scaffold provided very high surface area for interaction with bacterial cells, doping with Carbon Nano-tubes provided extra-ordinary conductivity to the scaffold!

c. Microbial-Enzyme Hybrid MFCs
In a recent research publication of April 2013, a scientific group from The University of New Mexico reported the use of laccase-modified air-breathing cathode, which catalyzed the reduction process for water production at the cathodic half. Media had lactate as carbon source. Shewanella oneidensis was used as the microbe that didn't need any mediator.

The coupling of waste water treatment process with electricity generation using the concept of MFC has been a big hit with many scientific groups across the globe. It is based upon the conversion of waste water treatment vessel into anode and connecting a cathode to it, making it a full-fledged Waste-Water-Treating & Electricity Production hybrid system.

There are numerous videos on sites like youtube citing the MFC models of various students and scientists across the globe. Each has it's own design and it's own efficiency. MFCs are indeed one of the simplest and yet amazing systems, and the best part is that even "you" can make it by hardly spending $2 on it!

The literature will keep updating on every development in the MFC domain, and I hope the next update comes from your side soon!

Here's a link to a channel on youtube, where a student has explained the details on making a robust MFC at Home!:

Enjoy!

Thanks
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Camouflaged Nano-Soldiers Battling Micro-Enemies

May 9, 2013, 6:57 pm
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Despite the discovery of new antibiotics, bacteria are becoming more and more antibiotic resistant. Most pathogenic strains have developed multi drug resistant mechanisms, making them increasingly difficult to destroy using available antibiotics. One such bacterial species is Methicillin-resistant Staphylococcus aureus, commonly known as MRSA, which poses a significant threat to public health. However, there may be an ideal antidote for this malady, scientists believe.

A recent study conducted by a group of researchers at the University of California, San Diego, reveals the possibility of using nano-sized agents to disarm microbial pathogens, such as MRSA, instead of killing them. This is accomplished using ‘nanosponges’ that absorb and neutralise the Pore-Forming Toxins (PFTs) produced by these bacteria. In an article published in the journal Nature Nanotechnology, April 2013, Professor Liangfang Zhang and the colleagues described the potential of using nanosponges for removing PFTs from the blood stream. They have successfully produced a “toxin absorbing nanosponge” by camouflaging a nanopolymer in red blood cell (RBC) membranes. Once injected into the blood, these fake red blood cells bind non-specifically to PFTs and deactivate them.

Pore-forming Toxins represent one of the most common weapons employed by the bacterial pathogens such as Staphylococcus aureus, Escherichia coli, Listeria monocytogenes, Bacillus anthracis, Streptococcus pyogenes and Streptococcus pneumoniae. These toxins form holes in the cell membranes of the hosts, thus allowing the ions and molecules inside the cell to flow out and water from the surrounding tissues to flow in. This causes the cell to lose its functionality and eventually results in cell death. Not only pathogenic bacteria, but also some animals such scorpions, snakes and bees also produce PFTs. Over 80 different types PFTs have been discovered so far and the variations in their molecular structure demand for specific treatments for individual toxins. However, this study demonstrated that these new toxin absorbing nanosponges can be used as broad spectrum anti-toxins against a wide variety of PFTs. Bacterial toxins extracted from S. aureus and S. pyogenes as well as a Pore Forming Toxin found in bee venom was used in this study and the nanosponges were shown to be effective against all the PFTs regardless of their origin.

These toxin absorbing nanosponges were produced by incorporating poly (lactic-co-glycolicacid)(PLGA) particles into vesicles of bilayered RBC membranes including both lipids and the surface proteins. The RBC membrane coating surrounding the nanopolymer mainly serves two purposes. First, it prevents the host immune system from destroying the nanopolymer. Since the nanosponge is disguised in a natural red blood cell membrane, the host immune system doesn’t identify it as an invader. It also makes the nanosponge a RBC look-alike and baits the toxin molecules into attaching to its surface. The nanopolymer core captures the toxin molecules, keeping them away from other cellular targets. It also stabilises the RBC membrane coating, enabling the nanosponge to survive longer in the circulation system, thereby increasing the efficacy of the nanosponge. The detained toxin molecules are detoxified and accumulated in the liver where they are eventually metabolised.

Here's a video that explains how these nanosponges work:




The researchers say that they are focusing mainly on using this new discovery for finding a treatment for MRSA infections. So far, the studies have been carried out using mouse models and further clinical investigations are required to be done in order to determine their performance within human systems.

Major drawback of these anti-venom nanosponges is that, although effective against PFTs, they cannot be used as a cure for diseases caused by other types of toxins such as neurotoxins. But their potential of functioning as universal antidote is certainly an advantage. Furthermore, owing to their minute size, these nanoparticles can freely circulate through the blood stream, consequently arresting a large number of toxin molecules.

Apart from being used as anti-toxins, nanosponges can be used in numerous applications such as cleaning up organic and inorganic spills in water, purification of drinking water, oxygen delivery system, drug carriers etc. In a previous study, a research team lead by Professor Liangfang Zhang studied the possibility of cloaking nanosponges in RBC skins for using them as vehicles for systemic drug delivery.

Source: http://www.nature.com/nnano/journal/vaop...13.54.html
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Pharmaceutical Biotechnology - Production of Proteins and Biopharming

May 9, 2013, 9:41 pm
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The use of biotechnology in both medicine and pharmaceutical industries is the most influential developments in the world of technology in this 21st century. In the effort to comprehend biology, to eradicate diseases and maintain a health and vigor, biotechnology has gone a notch higher in surmounting extreme in search of knowledge and manipulation of life. In order to achieve what biotechnology holds for pharmaceutical industries, tools necessary for identification of molecular structures, creation of active molecules and development of novel comprehensive therapies like immunotherapy and cellular or organismal therapy with genetically engineered cells. However, the huge amounts of data and information alone are not sufficient to lead to new molecular entities and novel therapies, since synthesizing millions of compounds will neither fill the universe of potential molecular structures nor allow identification of those three-dimensional structures specifically interacting with targets.

Biotechnology is central in almost all the pharmaceutical processes. It is widely applied to manipulate different biological chemicals to either actively or passively act as therapies to different kinds of conditions. Modern biotechnology is often associated with the use of genetically modified microorganisms such as Escherichia coli or yeast for the production of substances like antibiotics and synthetic insulin. It can also refer to transgenic animals or transgenic plants, such as Bt corn. Certain pharmaceutical products are also manufactured from genetically altered mammalian cells, such as Chinese Hamster Ovary cells (CHO). Another promising new biotechnology application is the development of plant-made pharmaceuticals. In fact biotechnology has made landmark discoveries in the field of diagnostics in the medical industry. For instance, women suffering from breast cancer whose cancer cells express the protein HER2 use Herceptin, the first drug approved for use with a matching diagnostic test.

Production of proteins
In addition to the classical production of naturally occurring proteins, such as insulin, growth hormones, blood-clotting factors, IFNs and growth factors, the new application of techniques in molecular biotechnology has enabled the synthesis of superior proteins through production of artificial genes or through directed evolution.

Insulin production
Production of genetically engineered human insulin was one of the first breakthroughs of biotechnology in the pharmaceutical industry. Insulin was first produced in Escherichia coli through recombinant DNA technology in 1978. This was done by producing artificial genes for each of the two protein chains that comprise the insulin molecule and inserting them into a plasmid. These exogenous insulin genes were then activated by lactose which were then inserted into Escherichia coli bacteria that rapidly produced insulin. It is widely used today as a therapeutic mechanism against patients suffering from diabetes mellitus (DM). More recently, researchers have succeeded in introducing the gene for human insulin into plants and in producing insulin in them, to be specific safflower. This technique is anticipated to reduce production costs thus affordable to patients.

Production of Human Blood Clotting Factors
Initially, blood clotting factors were produced from donated blood that was partially screened of HIV. However, with approval from FDA, production of human clotting factors was enhanced through Recombinant DNA technology. Human clotting factor ix was the first to be produced through recombinant DNA technology using transgenic Chinese hamster ovary cells in 1986. Plasmids containing the Factor IX gene, along with plasmids with a gene that codes for resistance to methotrexate, were inserted into Chinese hamster ovary cells via transfection. As the development in recombinant DNA technology advanced, FDA approved production human blood clotting Factor VIII using transgenic Chinese hamster ovary cells, the first such blood clotting factor produced using recombinant DNA technology.

Production of Antibiotics
Antibiotics are agents that kill bacteria, fungi and other compounds. In the previous years, the search for antibiotics has been largely restricted to well-known compound classes active against a standard set of drug tests. Although many effective compounds have been discovered, insufficient chemical variability (and lack of novel targets and target mechanisms) has been generated to prevent a serious escalation in clinical resistance. Recent advances in genomics have provided an opportunity to expand the range of potential drug targets and have facilitated a fundamental shift from direct antimicrobial screening programs toward rational target-based strategies.

The application of genome-based Technologies such as expression profiling and proteomics will lead to further changes in the drug discovery paradigm by combining the strengths and advantages of both screening strategies in a single program. With these advances in medicinal chemistry, most of today's antibiotics chemically are semi-synthetic modifications of various natural compounds.

Production of Human Growth Hormone.
Production of human growth hormone was first done in 1979 in Genentech using recombinant DNA technology. These scientists produced human growth hormone by inserting DNA coding for human growth hormone into a plasmid that was implanted in Escherichia coli bacteria. This gene that was inserted into the plasmid was created by reverse transcription of the mRNA found in pituitary glands to complementary DNA. Prior to this development, human growth hormone was extracted from the pituitary glands of cadavers, as animal growth hormones have no therapeutic value in humans.

Biopharming
The term molecular pharming or simply pharming refers to the use of genetic engineering to insert genes that code for useful pharmaceuticals into host animals or plants that would otherwise not express those genes, thus creating a genetically modified organism (GMO). This method has also been used to produce useful products in the pharmaceutical industries to produce a number of therapies to different diseases. Unlike the usual genetic engineering processes, this method is considered less demanding in terms of infrastructure and costs. In the 21st century, Proof of concept has been established for the production of many therapeutic proteins, including antibodies, blood products, cytokines, growth factors, hormones, recombinant enzymes and human and veterinary vaccines through pharming. In February 2009 the United States FDA granted marketing approval for the first drug to be produced in genetically modified livestock. The drug is called ATryn, which is an antithrombin protein purified from the milk of genetically modified goats. Additionally, a most recent treatment for Gaucher’s disease has been approved. This drug is produced in cultured transgenic carrots and tobacco cells.
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