World Congress and Expo on Applied Microbiology-2015

February 6, 2015, 1:29 am

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Theme: State-of-the-art Trends in Applied Microbial Industries, Biotech and Pharmaceuticals

Featuring 3 days of Scientific workshop, Technical symposium, Special sessions, Speaker & Poster session, and Industrial Expo

Microbiology Conference Detail: World Congress and Expo on Applied Microbiology 2015 is held with the support of international representatives and editorial members from  Journal of Vaccines & Vaccination (IF 1.51), Journal of Microbial & Biochemical Technology (IF 2.16), and The Journal of Advances in Genetic Engineering & Biotechnology. Conference proceedings will be published in the subsequent issue release. 2014 Microbiology Conference

Speaker and poster abstract guidelines: Abstract should be 250 words in length followed by the biography of presenting author of upto 100 words. All submitted abstracts will be thoroughly examined by an expert committee. It is recommended to make your submissions at the earliest to give enough feedback time. Final submissions for speaker and poster categories will be accepted only till April 30, 2015. Please request a sample abstract format at :  microbiology@conferenceseries.net


2015 Sessions,

Bacteriology, Virology & Mycology (BVM) - Classification of microbes both clinical and industrial has helped to identify the pathogens from symbionts (Session Chair: Dr Joachim Wink, Helmholtz Centre for Infection Research)

Pharmaceutical Industries - Fine tuned microbes are used to produce higher grade antibiotics, vaccines, vitamins, enzymes, dietary supplements and more

Industrial Microbiology - Through out the century science of fermentation and technology has helped beer breweries and fizzy drink factories earn billion around the world

Food Microbiology - Enzymes and microorganisms are used to produce fine quality consumables and also help to study the food spoilages and poisonings. A fine example of cutting edge billion dollar market

Marine Microbiology - Oceans underneath is filled with lifeforms of various sizes. Understanding and transforming their molecular biology for potential use is done with much greater excitement these days

Environmental Microbiology - With the help of bioremediation and biodegradation waste treatment plants has helped recycle the valuable products and safe disposal of hazardous byproducts

Agricultural Micrbiology - Studying the symbionts and soil nature has helped to produce the nutrient rich bio products. Organic food products has greater health benefits and high profit margins

Biofuels/Petroleum Microbiology-  More research on finding alternative energy is going, with some of the efforts showing promising results towards the expansion of this science (Session Chair: Armen H. Trchounian, Plants and Microbes Biotechnology)

                   
Academia / Industrial Participation

Microbiology 2015, Germany will witness around 300 and more attedees from Europe and other countries. Professors, Research fellows and scientific eminences will be presented. We will also have the expertise from Bacteriologists, Virologists, Marine biologists, Mycologist, Parasitologists, Instrumentation engineers, System biologists, Genetic and protein engineers, Food processing experts, Soil and agricultural biologist, Ecologist, Chairman/Vice-chairman of industries and other experts of relevant field.

Exhibition, B2B Partnering & Event Collaboration

Microbiology 2015, Germany has exhibitor spaces available for product promotion by industrial exhibitors or act as the potential sponsor to introduce products of academia, industrial and field applications. Exhibitor booths are served on First come First serve basis depending on the space availability.  Timely notification to the organizers is highly recommended to make appropriate arrangements. Please call/e-mail to the event organizers for further details.

  Microbiology-2015_ConferenceGuide new.pdf   (Size: 669.55 KB / Downloads: 1)

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I am forced to study at home,can you recommend me where to start?

February 8, 2015, 2:41 am

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Hello guys
I am studying molecullar and cellular biotechnology in university,since a couple of months.I feel that I am hardly learning anything useful.I am not from the U.S.A.The education standart of my university regarding my study subject seems to be very,very low.Since I am planning to go abroad for my masters,and I am pretty sure that,as things are going now,I never could qualify,I try to learn mostly at home.The problem is,I just don't know where to start,what I have to know :-( .

I always encounter texts that seem to be too advanced,too offtopic.

So,to my question(sorry that it took so long)

If I plan to study molecullar and cellular biotechnology at home,from what basic books do i have to start?to which books should i advance?I am truly confused.I hope somebody has advice.Thanks!

The last book I read was "kuby immunology".I am sure it would be useful in the future,but I doubt it is a good place to start.
Another book I took a look at (today) was
"Introduction to Molecular Biotechnology- Fundamentals, Methods and Applications, An - Michael Wink"

But this seems too complicated to start with too.However,I may be in the wrong and this may be the "standard".I really don't know,I hope you guys have advice :L

about MS course in electronics engineering

February 8, 2015, 7:06 am

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Sir,
I am going to complete b-tech in ECE (Electronics & Communication Engineering) stream in 2015 with aggregate of 74(approximated)...
I wrote GATE exam and i will get a score of 35 out of 100 marks.......

Will i eligible to get MS seat in NUS/NTU in singapore in electronics engineering...?
what are websites useful to get information about MS course through GATE...?
wHAT ARE THE JOB OPPOTUNITIES GOING TO GET IN SINGAPORE BASED ON ELECTRONICS ENGINNERING?
wHEN/where TO APPLY FOR MS in singapore universites?


Regards
phanikumar paruchuri

whats best to do after BE in biotechnology?

February 9, 2015, 8:56 pm

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Hello everyone,
I'm presently in final semester of my engineering in biotechnology. I'm a little confused about what to do next. Whats good MS-bioinformatics or MS-molecular biology. Or should I go for combined Ms-phd program? I have given my GRE exam and got 286. Kindly help me out.

Athens Research and Technology

February 11, 2015, 7:35 am

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Athens Research and Technology is a biotechnology company based in Athens, GA, USA that specializes in the production of purified human proteins. We provide our self-manufactured products including custom protein solutions to major biopharmaceutical companies and research laboratories all over the world. ART produces purified lipoproteins, enzymes, transferrin, antibodies, etc. from a variety of different sources, but mainly working with human plasma. Athens Research is a small local company that operates on a global scale, so utmost customer satisfaction is delivered for every single order. As a primary manufacturer, our prices are lower than any other prices for the same product than any other vendor in the biotech market place.

To find more information and contact info, please visit http://www.athensresearch.com

To find more information regarding the products and services we provide, please visit http://www.athensresearch.com/produts/all.

My Daughter studying Bsc Bio Tech

February 13, 2015, 1:10 am

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Dear Sir

My Daughter is studying Bsc Bii-Tech and she is in 4th Sem.Pls guide what she should do post completing her Bsc.How she can brigten her job avenues and what field she should choose.

Regards

Achal

2 Positions for Master in Environmental Engineering

February 18, 2015, 3:49 am

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Two Master research positions pertaining to degree Master in Environmental Engineering are available in my lab at East China Normal University, Shanghai. Interested candidates should email me with their latest CV at varenyam@gmail.com. Fellowship: USD 600 per month, free international dormitory, waived fee plus additional advantages.

GenScript Licenses CRISPR/Cas9 gene editing technology from the Broad Institute

February 28, 2015, 1:09 am

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GenScript USA Inc, a leading biology CRO and its affiliates announced today that they have entered into a non-exclusive license agreement with the Broad Institute of MIT and Harvard to strengthen their existing GenCRISPR™ services portfolio with the set of extensive intellectual properties and technologies related to CRISPR/Cas9 genome editing systems from the Broad Institute. 

GenScript is a leading provider of CRISPR genome editing products and services. Since June 2013, GenScript began developing GenCRISPR™ genome editing services, including gRNA design and constructs and CRISPR/Cas9-based cell line engineering, producing case studies of validated knock-out and knock-in cell lines, and building a bioinformatics tool to aid in the design of gRNAs. The aim is to bring GenScript clients the best quality service and access to the latest advances in CRISPR/Cas9 related technologies. The Broad Institute’s vast CRISPR/Cas9 IP portfolio will be fully utilized to launch new CRISPR-related products and services to satisfy the research and drug discovery needs of GenScript clients.

Dr. Chuan-Chu Chou, Senior Vice President of GenScript comments “CRISPR/Cas9 has great potential to impact research and medicine. Our goal is to provide researchers with a one stop solution for all their CRISPR needs, from gRNA design to cell line engineering. We are very excited to enter this licensing agreement with the Broad. We share Dr. Feng Zhang and the Broad Institute’s vision to make CRISPR accessible to all researchers in order to help make research easy.”

 

About the Broad Institute of MIT and Harvard

The Eli and Edythe L. Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods, and data openly to the entire scientific community.

Founded by MIT, Harvard, and its affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide. For further information about the Broad Institute, go to http://broadinstitute.org.

About GenScript

Based in Piscataway, New Jersey, GenScript is a leading gene, peptide, protein and antibody research partner for fundamental life science research, translational biomedical research, and early stage pharmaceutical development. Since its establishment in 2002, GenScript has grown into a global Contract Research Organization that provides services and products to scientists in 86 countries worldwide. The company has built a best-in-class capacity and capability for biological research services encompassing gene synthesis and molecular biology, peptide synthesis, custom antibodies, protein expression, antibody and protein engineering, and in vitro and in vivo pharmacology. For more information, visit http://www.genscript.com.

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protein electrophoresis SDS-page

March 2, 2015, 12:32 am

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1. I run protein SDS-page. The beginning, the protein bands were appearance, but then running back, i did not see any band. Who answer me why? I asked my teacher, he said that contents of protein not enough. But after condensed sample that shows no band.
2. I run SDS-page according to the method of Laemmli (1970), I mixed stacking gel 3%, it was polymerized about 15 minutes . But after I also do the same protocol that was not polymerize to 1 hour. Who can explain to me?
Here are recipes stacking gel 3% of Laemmli protocol:
2.5 ml 4X Stacking Gel Buffer
6.5 ml dH2O
1.0 ml acrylamide (29: 1)
200 microliter of 10% APS
20 microliter of TEMED
* 4X Stacking Gel Buffer
0.5 M Tris pH 6.8 6,06g, pH to 6.8 with HCl
0.4% SDS 0.4 g SDS
up to 100 ml with dH2O
3. Protein of salted squid less protein of fresh squid. Is protein of salted squid went outside in salted environment?
Thank you very much!

Blood-based cancer diagnosis: promising new strategy

March 6, 2015, 6:32 am

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A new strategy for improved cancer detection via blood-based diagnosis has been described in a recent study in the journal Proceedings of the National Academy of Sciences (PNAS). The study comes from a team of researchers based in Stanford University and in National Yang-Ming University in Taiwan.

Early cancer detection can lead to dramatically improved effectiveness of treatment strategies. Blood-based diagnosis would be a major advantage in this regard, but despite intensive research efforts over decades, many apparently promising blood biomarkers have failed clinically. Problems such as variability of cancer biomarker expression by non-malignant cells and heterogeneity among tumours have proved to be frustratingly intractable.

In the current study, the research team attempted to overcome these issues by artificially engineering the tumour cells to express a reporter which is not normally expressed in any tissue. The researchers used nonviral safe vectors called “tumor-activatable minicircles”. These used the pan-tumour–specific survivin promoter to drive expression of a secretable reporter. The minicircles were systemically administered to mice that were expressing human melanoma metastases and also to tumour-free mice. The results indicated that by measuring blood reporter levels, tumour-bearing mice could be reliably distinguished from tumour-free mice for up to two weeks. Furthermore, tumour burden in the lungs correlated with cumulative reporter levels, indicating that the extent of disease progression could also be determined. 
 
The study authors suggested that their test could first be used in patients with a high risk for tumour recurrence, then for diagnostic screening of high-risk populations and, if proven safe and effective, for the general population. They concluded: “Our system represents an alternative paradigm for improved cancer detection and could enable more timely interventions to combat this devastating disease.”

Reference: Ronald JA, Chuang H-Y, Dragulescu-Andrasi A, Hori SS, Gambhir SS. Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker. PNAS (2015) doi: 10.1073/pnas.1414156112

Oil-Eating Bacteria to Clean up Oil Spills

March 6, 2015, 9:28 am

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One of the biggest issue affecting health, agriculture, environment, financial sectors is recent times is the “oil-spill”. Scientists from various parts of the world are engaged in research towards oil spill clean ups. Europe has reported the sequenced genome of an oil-eating bacterium that has the ability to quickly and efficiently metabolized oil and cleans up oil spills.

In the past, bacteria were experimentally applied to clean up the 11 million gallons of crude oil spilled by the Exxon Valdez ashore off the coast of Alaska. While it did not make much variation back then, it is now that scientists presented the entire blueprint of the oil-starving bacteria: Alcanivorax borkumensis, with the facility to optimize the conditions for these organisms making them capable of soaking up the hundreds of millions of liters of oil that penetrate the water bodies each year.

According to Vitor Martins dos Santos of the Helmholtz Center for Infection Research (formerly the German Research Center for Biotechnology) in Braunschweig, Germany one of the co-leaders of the international project, with the entire blueprint for Alcanivorax borkumensis, scientists expects a better understanding of the specific physiological mechanism that facilitate the organism to survive entirely on hydrocarbons. The 2,755 sequenced gene of the organism has been illustrated in the journal ‘Nature Biotechnology’.

While, some bacteria have the ability to metabolize oil, but until now exploiting these potential for remediation has been hesitated. Although the oil-consuming bacteria quite uncommon in uncontaminated surroundings, they are abundant in presence of oil; in oil spills A. borkumensis makes up  to 90 % of the microbial populations. It is important to create the optimized conditions for these bacteria to grow faster in oil contaminated areas and metabolize them efficiently.  According to de Lorenzo, it has now become a standard practice to include oil-soluble forms of phosphorous and nitrogen to oil spills. However, actual understanding of the specific nutrients required by the bacteria is still awaited.

Since bacterial method of remediation was not quite successful, oil spill cleanup rely much on the use of physical removal of oil with boom and application of chemical dispersants to split the remains. This method is not much acceptable since physically recovery of oil is quite expensive, and chemicals used along with the remaining oil that might not be quite visible are harmful to the environment .

The genomic information obtained from decoding the genome of the organism A. borkumensis  has disclosed the mechanism of molecular transport that facilitated the bacteria to procure nutrient from its environment. The research also help recognize the plethora of genes responsible for the production of the bacterial oxidative enzymes required for oil degradation, that should enable the researchers easier to find other organisms with capabilities alike.

Such organisms will be essential since A. borkumensis has the ability to metabolize compounds of low molecular weight only, that add up to only 70 % of crude oil. Therefore, finding out organisms that could consume the remaining high-molecular-weight compounds, is quite essential. Research towards sequencing of other oil-eating bacteria is in progress in the United States, Japan, Australia.

Tumor Fighting Immune Cells to Attack Cancer

March 6, 2015, 9:31 am

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An extensive study on a group of tumor-forming immune system cells was carried out by the scientists at UCLA’s Jonsson Cancer Center in order to find and demolish dangerous melanomas. According to Dr. Antoni Ribas, senior author of the investigation, the team focused on developing the immune system through genetic engineering to kill cancer cells and represent the function of the immune system at the same moment.

According to the investigation, the full grown melanomas in mice utilize a dormant HIV-like virus that makes T- cell receptor armed lymphocytes the destroyer of cancerous cells. The genetically engineered lymphocytes were marked with a reporter gene inserted into to cells that during PET scanning shine “hot” which help the scientists locate the lymphocytes following their injection into the blood stream, move through the lymph nodes and the lungs, and arrive in on the lumps anywhere they may be situated in the body. Although the group constructed and introduced one million genetically engineered lymphocytes approximately into a mouse however they stated that humans require about one billion tumor-seeking cells to combat cancer. The researchers expect to implement the process on human, within approximately one year.

Usually, the cancerous cells are not recognized as enemies by the immune system. The genetically engineered antigen-specific T cell receptors inserted to look out for a tumor antigen on the melanoma cell surface - effectively uncover the cancerous cells, disclosing them as fatal attackers that must be killed.

Imaging the engineered T cells while they look for and hit the cancer cells, the researchers can closely monitor the progression of the immune system during its fight against malignancies that could then improvise the monitoring process to treat melanoma in patients.

The study showed that within two to three days the cells started fighting against the melanoma following their  injection into the bloodstreams of the mice. The mice were imaged for 10 days at regular intervals to ensure that the cancerous cells were indeed killed by the lymphocytes. However, the process of killing the malignant cells might take more number of days in human system.

If following insertion of genetically engineered T cells, a patient's tumor fails to react well, researchers could verify by PET scanning if the cells did successfully reach the tumor site and also even if they did, whether they performed as was anticipated. A proper observation of the immune response also present evidences on methods of improved engineering of the lymphocytes to make them more effective in seeking out and attacking the tumors.

Engineered Tobacco Plants as Biofuel

March 6, 2015, 9:33 am

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Detection of a novel method to increase oil in tobacco plant by the researchers at the Biotechnology Foundation Laboratories at Thomas Jefferson University is a major breakthrough towards production of biofuel from these plants. Since tobacco plants are very efficient producer of biofuel, use of such plants can prevent exploitation of other agricultural crop.  However a major challenge to the researchers was the presence of the precious oil mostly in tobacco seeds while the tobacco plants can produce about 600 kg of seeds per acre only. 


Tobacco seeds comprises of nearly  40 percent oil per dry weight. Nevertheless, genetic engineering of the plants can somehow solve this problem by enabling the leaves to produce more oil. One of the project’s researchers, Dr. Andrianov, reported modification of the tobacco plants so as to increase oil production up to  20-fold. According to Andrianov,  a promising and effective ‘energy plant’ platform being provided by tobacco, that also could act as a model for the utilization of other plants with high-biomass content required for production of biofuel. Dr. Andrianov stated that tobacco is quite an attractive plant for biofuel production that goes with the  idea of using plants not required for food production.  Plants were genetically engineered to make the leaves more effective in oil production. It has been found that leaves of tobacco plant contain 1.7 percent to 4 percent of oil per dry weight. 


Genetic engineering resulted in over-expression of one of the two genes: the diacyglycerol acytransferase (DGAT) gene or the LEAFY COTYLEDON 2 (LEC2) gene. Modification of the DGAT gene increased oil production up to 5.8 percent per dry weight in the leaves, which is nearly two-fold of the  oil produced normally. Modification of LEC2 gene resulted in6.8 percent of oil production per dry weight. Dr. Andrianov and Dr. Nikolai Borisjuk, Jefferson Biotechnology Foundation Laboratories co-authored the paper. Hilary Koprowski, M.D., director of the Jefferson Biotechnology Foundation Laboratories, also contributed to the research.

Cheap, Effective Genome Sequencing Technology

March 6, 2015, 9:37 am

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Application of personalized healthcare for treatment and prevention of several diseases efficiently is in increasing demand in recent times. One of the most vital tools for personalized medicine is Genome sequencing, since it offers the necessary genetic information for identification and management of particular diseases. A nano-pore based sequencer with the aim of directly reading and decoding human DNA more efficiently, quickly and formidably was developed by Roche, a leader in research-focused healthcare and biotechnology, in collaboration with IBM (Armonk, NY, USA), a leading player in the areas information technology, microelectronics,and computational biology.Their target is to decrease the sequencing cost of an individual’s genome to between $100 and $1000 as compared to $9,500-$19,500 charged by companies such as San Diego’s Illumina, one of the leaders in analysis of array-based solutions for DNA, RNA and protein which is already a radical drop in comparison to its previous $48,000 price mark.

With the aim of reducing the cost so drastically, researchers working with Roche and IBM are focusing on sequencing of true single molecule that can decode DNA molecules, since they are stranded all the way through a nanometer sized pore in a silicon chip. This is a significant approach towards cost reduction, scalability, throughput, and speed in comparison to other sequencing technologies available currently or in the process.

According to the agreement, Roche will be funding the development of the technology continuously at IBM and offer additional resources in collaboration with Roche's sequencing contributory, 454 Life Sciences. All of the technology based products will be developed and marketed by Roche.

According to Ajay Royyuru, senior manager of the department of computational biology at IBM, with the integration of biotechnology, computational biology, and nanotechnology, a system is being developed that can efficiently and accurately translate DNA into genetic information which is quite significant medically. To slow down and control the motion of DNA through the nano-pore is a major challenge of all nano-pore based technologies that the companies are trying to overcome. This is highly desirable for an accurate decoding of the DNA sequence."

According to Manfred Baier, head of Roche applied science, sequencing is an essential tool for personalized healthcare that offers the basic genetic information essential for diagnosis and treatment of various diseases. This potent technology along with the mutual strengths of Roche and IBM– will construct cost effective whole genome sequencing with faster availability to the marketplace than was earlier thought possible.

Stem cell culturing without the use of animal substances

March 6, 2015, 9:38 am

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Human embryonic stem cells for the first time have been cultured at chemically controlled conditions exclusive of the application of animal material, which is a vital aspect for future clinical uses.

Scientists and researchers at Sweden’s Karolinska Institutet, produced human stem cells devoid of other cells from animals, in an entirely chemically-defined ambiance. So far embryonic stem cells have been cultured by means of animal proteins, excluding the possibility of applying them for human treatment. At present, they have been cultivated on a matrix of a distinct human protein: laminin-511, a component of our connective tissue, a matrix that helps cell to connect to. This is a highly promising research since it may enable scientists to build up various cell types that can lead to management of various human diseases.

It is possible to transform the embryonic stem cells into other cell type in the body and can be potentially applied for replacement of abnormal cells. However one of the major setbacks is that it is quite hard to avoid contamination while developing and culturing human embryonic stem cells. At present they are cultured with the help of animal proteins, which overrules the possibility of ensuing application in the treatment of humans. On the other hand, it is possible to culture stem cells on other human cells, recognized as feeder cells, however these cells discharge huge amount of uncontrolled proteins thereby resulting in contradictory research results.

With the discovery of the process of culturing the cells on a matrix of a single human protein:   it has now become possible to generate huge quantities of human embryonic stem cells in a chemically defined. In the newly formed embryo, the protein laminin-511 is required to keep stem cells as stem cells. Laminin is needed with the once the embryo starts developing.  So far, since it is quite not possible to extract and produce laminin from tissues it becomes difficult for the researchers to access various forms of laminin . However over the past couple of decades, a research group headed by Karl Tryggvason's  has cloned the genes for most of the laminins in human, investigated their biological role, illustrated two genetic diseases and, at present  applying gene technology, generated various retypes of laminin. Using recombinant techniques the researchers produced the laminin-511. The scientists and researchers at the Harvard Stem Cell Institute also reported that in the similar manner it is possible to culture cells known as reprogrammed stem cells, that has been transformed "back" from tissue cells to stem cells.

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Genetic engineering produces TB-resistant cattle

March 9, 2015, 3:18 am

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A study from scientists in the Ministry of Agriculture in Northwest A&F University, Yangling, China has described production of a herd of genetically engineered cattle with improved resistance to low levels of bovine tuberculosis (TB) infection. The study was published last week in the journal Proceedings of the National Academy of Sciences. The study authors commented: "Our results contribute to the control and prevention of bovine tuberculosis and provide a previously unidentified insight into breeding animals for disease resistance."

Bovine TB is a risk in many parts of the world, including the UK, New Zealand and parts of Africa and Asia. It led to culling of over 26,000 cattle in the UK alone in 2013. It is a chronic infectious disease which affects a broad range of mammalian hosts and is considered a particularly serious threat to agriculture in many less-developed countries.

In the current study, the research team used a genetic engineering system called the transcription activator-like effector nickase (TALEN) system. This enabled them to introduce a mouse gene called SP110 to a specific location in the bovine genome in Holstein–Friesian cattle. Polymorphisms in SP110 have been associated with risk of developing TB in mice, humans and cattle. The results indicated that this modification produced tuberculosis-resistant cattle. Results of both in vitro and in vivo experiments suggested that the transgenic cattle were able to control the growth and multiplication of Mycobacterium bovis, kill the bacteria via apoptosis after infection, and efficiently resist low dose infection with M. bovis transmitted from tuberculous cattle in nature. Use of the TALEN system to ‘knock in’ the mouse SP110 gene thus resulted in a heritable genome modification which was facilitative of TB resistance.

Prof Heiner Niemann, of the Institute of Farm Animal Genetics at Friedrich-Loeffler-Institut, Germany, said that the findings of the study were another step towards the creation of disease resistant livestock animals based on advanced genetic tools. However, he cautioned: "Whether this approach protects cows against TB infection when exposed to high doses of the pathogen remains to be determined."

References:
Wu H et al. (2015). TALE nickase-mediated SP110 knockin endows cattle with increased resistance to tuberculosis. PNAS doi: 10.1073/pnas.1421587112
Ruiz-Larranaga O et al. (2010).  SP110 as a novel susceptibility gene for Mycobacterium avium subspecies paratuberculosis infection in cattle. Journal of Dairy Science 93(12):5950-8. DOI: 10.3168/jds.2010-3340

‘Heart-on-a-chip’ and potential for new drug testing.

March 9, 2015, 3:59 am

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A new ‘heart-on-a-chip’ system may provide a highly effective in vitro model for screening of cardiovascular medications and for testing cardiotoxicity of other pharmaceuticals, according to a new study in the journal Scientific Reports. The cardiac microphysiological system (MPS) was developed by a research team led by bioengineering professor Kevin Healy of the University of California at Berkeley.

Currently, new drug development relies heavily on animal models and animal-derived cell lines. This makes the process inefficient and expensive, as inter-species differences in key biological pathways and pharmacokinetic properties mean that animal models cannot completely mimic human physiology. Ion channels, for example, are key for conducting cardiac electrical currents and can vary widely in type and number between humans and animals. Prof Healy explained: "Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans." These types of differences lead to issues including inaccurate prediction of human cardiotoxicity of new drugs. As a result, about one third of pharmaceuticals withdrawals due to safety concerns are related to cardiotoxicity. On average, a new drug takes 10-15 years and approximately $5 billion to produce, with many of the costs being incurred in the preclinical and clinical development. The current study aimed to address the gap in availability of reliable in vitro systems based on a human genetic background for prediction of cardiac effects of drugs.

In the current study, the research team used human induced pluripotent stem cells to derive human cardiac tissue. Differentiated human heart cells were added to the loading area of the cardiac MPS structure, which was designed to be comparable to the geometry and spacing of connective tissue fibres in a human heart. Microfluidic channels were used as models for blood vessels, to mimic nutrient and drug exchange by diffusion. The confined geometry of the system allowed cells to be aligned in multiple layers and in a single direction, making it physiologically relevant. Lead author Anurag Mathur, a postdoctoral scholar in Prof Healy's lab explained: "This system is not a simple cell culture where tissue is being bathed in a static bath of liquid. We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs."

Within 24 hours of loading the heart cells, they began beating independently at a normal physiological rate of 55 to 80 beats per minute. In order to test the responsiveness of their system, the research team used four well-characterised cardiovascular drugs, namely isoproterenol, E-4031, verapamil and metoprolol and measured changes in the heart tissue's beat rate. Beat rate changes were predictable and consistent with data on tissue scale references as opposed to cellular scale studies.

The study authors noted, for example, that the system could be adapted for modelling of human genetic diseases or for individual drug screening. They are also interested in the system’s potential for study of multi-organ interactions. They envisage accommodating hundreds of microphysiological cell culture systems on a single standard tissue culture plate. Prof Healy explained: "Linking heart and liver tissue would allow us to determine whether a drug that initially works fine in the heart might later be metabolized by the liver in a way that would be toxic." The viability and functionality of the engineered heart tissue over many weeks adds to the system’s versatility and suggest that the system could be used for assessing various drugs. In conclusion, the authors of the study: “anticipate the widespread adoption of MPSs for drug screening and disease modelling.”

Reference: Mathur A. et al. (2015).  Human iPSC-based Cardiac Microphysiological System for Drug Screening Applications. Scientific Reports  5, Article number: 8883. doi:10.1038/srep08883

Press release available at: http://www.eurekalert.org/pub_releases/2015-03/uoc--bph030615.php

Positive phase 3 trial results for Trimel’s Natesto testosterone nasal gel

March 9, 2015, 4:30 am

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Results of a phase 3 clinical trial of a new testosterone nasal gel called Natesto were presented on Saturday 7th March at the Endocrine Society's 97th annual meeting in San Diego. The gel is manufactured by Trimel Pharmaceuticals and the phase 3 results indicate that it raises low testosterone levels in men to normal, with few side effects. Lead study author Dr Alan Rogol of the University of Virginia and a consultant to Trimel said: "The unique delivery system makes this a convenient and easy-to-use, self-administered form of testosterone to treat adult males with hypogonadism [low testosterone]. Also important is that intranasal testosterone minimizes the risk of unwanted secondary exposure of testosterone to women or children." The latter point is important as there is a risk of transfer to others from testosterone products applied to the skin. Natesto, on the other hand, is designed to be administered in specified amounts by a multiple-dose pump dispenser applied to the nostrils.

Natesto was approved last May by the U.S. Food and Drug Administration. In the phase 3 trial presented at the Endocrine Society meeting, effectiveness and safety of the nasal gel was assessed in 306 men with hypogonadism attending 39 U.S. outpatient centres. Men were randomly assigned to use Natesto for 90 days in both nostrils either twice a day (228 men) or three times a day (78 men) in order to determine the most effective dose. They remained on the drug for another 90 or 180 days for evaluation of both tolerance and effects of treatment.

The results indicated that after 90 days, blood testosterone levels were in the normal range for 90% of the men who applied the gel three times a day as opposed to 71% of the twice-daily users. This informed the decision of Trimel to recommend dosing of three times a day in each nostril, to achieve a total daily dose of 33 mg. No serious adverse effects were noted in either dosing group and rates of problems of tolerance of the gel were low, with 3.7% of the thrice-daily users discontinuing the drug due to side-effects. Treatment results in significantly improved erectile function and mood. 84% of the 99 men who completed a survey on their experience with the drug, reported feeling confident that they were correctly using the applicator within two days of beginning treatment. Dr Rogol concluded: "These results indicate that testosterone nasal gel is an effective and practical alternative to other available testosterone replacement therapy products."

Reference: Rogol A. A Novel Testosterone Nasal Gel Formulation Normalizes Androgen Levels in Hypogonadal Men. Presented March 7 2013, The Endocrine Society's 97th Annual Meeting (San Diego).

Press release available at: http://www.eurekalert.org/pub_releases/2015-03/tes-tng030615.php

Sluggish Rubisco enzyme needs appropriate chaperone for improved plant growth

March 9, 2015, 7:04 am

≫ Next: Immunity genes associated with post-traumatic stress development

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There is currently widespread interest in development and implementation of strategies to improve crop productivity and address worldwide food-security concerns. One long-standing research challenge in this field has been the task of enhancing catalysis of the photosynthetic CO2-fixing plant enzyme Rubisco. Rubisco is the most abundant protein on Earth and is responsible for conversion of carbon dioxide to organic compounds. However, Rubisco is famously inefficient in its enzyme activity.

A new study from scientists based in the Australian National University and in the University of Wollongong, also in Australia, may have come up with the solution. The research team used genetic engineering to introduce a modified version of one of Rubisco's partner chaperone proteins, RAF1. Phylogenetic analysis revealed that Rubisco and RAF-1 had evolved together and when modified Rubisco is introduced into plants, it requires a complementary modified RAF-1. When both modified tobacco Rubisco and RAF-1 were introduced into the model Arabidopsis plant, plants were produced that had increased Rubisco biogenesis and improved leaf phosynthesis and growth. The study is published in the journal Proceedings of the National Academy of Sciences.

The current study results suggest that the issues encountered in improving Rubisco performance in other studies may have arisen from misunderstanding of how highly complex the structure of Rubisco is. The enzyme has 16 pieces that requires the assistance of more than 12 other proteins, including the RAF-1 chaperone, for correct assembly. Research team leader Dr Spencer Whitney of the Australian National University explained the significance of the study in terms of food-security: "Understanding the partnership with RAF1 has important implications with regard to ongoing efforts to accelerate the sluggish activity of Rubisco - a key goal for improving crop productivity. In a world with increasing demands for food, this is a milestone towards increasing the photosynthetic rate in crop plants that rely heavily on Rubisco." These would include staple food crops such as wheat and rice, as well as other important commercial crops such as cotton. Dr Whitney added: "The finding also explains why our prior attempts to insert more efficient versions of Rubisco from some algae into plant leaves have failed - they require different chaperones to those available in leaf cells."

The authors concluded that the outcomes of their study: “have application to the growing interest into identifying and implementing strategies to supercharge photosynthesis to improve crop productivity and stem global food-security concerns.”

Reference: Whitney SM, Birch R, Kelso C, Beck JL, Kapralov MV. Improving recombinant Rubisco biogenesis, plant photosynthesis and growth by coexpressing its ancillary RAF1 chaperone. PNAS (Early edition) (2015). doi: 10.1073/pnas.1420536112

Press release available at: http://www.eurekalert.org/pub_releases/2015-03/anu-spo030215.php
 
 

Immunity genes associated with post-traumatic stress development

March 10, 2015, 4:08 am

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Post-traumatic stress disorder (PTSD) is a complex psychiatric disorder which is particularly challenging to study given the presence or trigger of a traumatic event, for example serving in a combat zone. Researchers have succeeded in a new study in identifying discrete groups of co-regulated genes associated with PTSD development in blood samples from U.S. Marines before and after deployment in combat zones. The relevant genes are associated with immune responsiveness.

The study comes from researchers at the Veterans Affairs San Diego Healthcare System and University of California, San Diego School of Medicine, with colleagues in New York and the United Kingdom. Co-senior author Dr Christopher H. Woelk, reader in genomics and bioinformatics at University of Southampton and assistant adjunct professor at UC San Diego School of Medicine, explained: "The odds of obtaining a sample both before and after a traumatic event are incredibly small. Under this experimental design, not only can we identify differences between U.S. Marines with PTSD and without, but we can go back in time, so to speak, to see if any of the Marines who eventually developed PTSD contain prognostic signatures that might be indicative of eventual PTSD emergence. In this vein, we are able to start labeling findings as being putatively 'causal' in nature." The study is published in an advanced online version in the March 10 issue of the journal Molecular Psychiatry.

In the study, the research team used a system called whole-transcriptome RNA-Seq gene expression to examine gene expression from blood leukocyte samples taken from 188 U.S. Marines both pre- and post-deployment to conflict zones. The researchers identified discrete co-expression modules (groups of co-regulated genes). One module was identified at both pre- and post-deployment as containing proposed causal PTSD development signatures. This module was enriched in innate-immune response and interferon-signalling genes. Interferons are normally released by host cells in response to infections. The results were replicated in a second independent sample of 96 U.S. Marines. A second module was identified post-deployment containing PTSD resiliency signatures. This module was rich in genes associated with haemostasis and wound healing.

Co-author Dr Dewleen G. Baker of the VA Center of Excellence for Stress and Mental Health and Department of Psychiatry at UC San Diego commented:  "What's interesting is that molecular signatures of innate immunity and interferon signaling were identified both after developing PTSD as well as before developing PTSD. The question to ask is what's stimulating an interferon response prior to PTSD development. The answer could be any number of factors, ranging from a simple explanation of increased anticipatory stress prior to deployment or more complex scenarios where individuals may have a higher viral load. It's a question for future studies."
The researchers conclude that their findings suggest two lines of further enquiry. The first would be development of a blood panel of predictive biomarkers for identification of individuals at greater risk of PTSD development. The second would be utilising the molecular information from blood samples for design of targeted therapies for either treatment or prevention of PTSD.

References
Breen MS, Maihofer AX, Glatt SJ, Tylee DS, Chandler SD, Tsuang MT, Risbrough VB, Baker DG, O'Connor DT, Nievergelt CM, Woelk CH. Gene networks specific for innate immunity define post-traumatic stress disorder. Molecular Psychiatry advance online publication 10 March 2015; doi: 10.1038/mp.2015.9

Press release available at: http://www.eurekalert.org/pub_releases/2015-03/uoc--gnf030415.php