In deep sea waters, over a mile below the surface, microbes rely on inorganic compounds such as sulphur as an energy source rather than sunshine. There, in the mineral-rich waters that cascade from hypothermal vents (seafloor hot springs) viruses prey on the SUP05 bacterium to plunder the energy released from its sulphur reserves. SUP05 is the gene that is responsible for energy extraction from sulphur. This relationship between the bacteria and the virus has featured exchange of genes as the viral DNA contains genes closely related to the bacterial SUP05 genes. This has important implications for implicating viruses as agents of evolution as the viruses then force the SUP05 bacteria to use viral SUP05-like genes to process elemental sulphur. These are the findings of a paper published online in the journal Science on May 1st from researchers in the University of Michigan.

Microbial interactions like these have been previously observed in shallow to mid-depth ocean waters featuring photosynthetic bacteria. The current study used an unmanned submarine at a depth of over 6,000 feet, to obtain DNA samples from deep-sea microbes at hydrothermal vent sites. These samples were collected on trips to the Eastern Lau Spreading Centre in the Western Pacific and the Guaymas Basin in the Gulf of California.

Having obtained the samples, the research team set about reconstructing the viral and bacterial genomes by combining information from DNA snippets retrieved at six sites. As well as confirming the presence of the common sulphur-consuming bacterium SUP05, they discovered genes from five viruses that had never been previously identified. The most surprising result was that the viral DNA contained genes closely related to the bacterial SUP05 genes that are responsible for energy extraction from sulphur.

Co-author on the study, Dr Melissa Duhaime explains the viral strategy: "We hypothesize that the viruses enhance bacterial consumption of this elemental sulphur, to the benefit of the viruses.” First author Karthik Anantharaman continues: “We suspect that these viruses are essentially hijacking bacterial cells and getting them to consume elemental sulphur so the viruses can propagate themselves." It is not known for sure how the SUP05-like genes ended up in the viruses. However, the researchers hypothesise that the exchange occurred during an ancient microbial interaction. Senior author Gregory J. Dick says: "There seems to have been an exchange of genes, which implicates the viruses as an agent of evolution. That's interesting from an evolutionary biology standpoint."

The findings are important as oxygen-starved zones are growing in the world’s oceans due to global environmental changes. This means that bacteria such as SUP05 and the viruses that prey on them are likely to expand their range. These bacteria may generate nitrous oxide, a greenhouse gas. It is important to gain a full understanding of the sulphur cycle and the bacterial-viral relationships.

Sources
Anantharaman, K., Duhaime, M. B., Breier, J. A., Wendt, K., Toner, B. M., and Dick, G. J. (2014). Sulfur oxidation genes in diverse Deep-Sea viruses. Science. http://dx.doi.org/10.1126/science.1252229 [Accessed 2 May 2014]

Press release: University of Michigan; available at http://www.eurekalert.org/pub_releases/2...042814.php [Accessed 2 May 2014]

There is currently widespread interest in the potential of dental pulp stem cells from teeth as a source of neurons for treatment of stroke and traumatic brain injury. In order to make this a reality, a mouse model of neural stem cell transplantation would be a very useful pre-clinical tool. A research team from the University of Adelaide in Australia have developed a system for culturing murine dental pulp stem cells in conditions in which they developed into networks of neuron-like cells. The study is published in the journal Stem Cell Research & Therapy.

A stroke is the result of damage to blood vessels carrying oxygen and nutrients to the brain which causes interruption of blood supply to part of the brain. This can result in damage to or destruction of brain cells (neurons) that control body functions such as movement, ability to speak or mental processes. Dr Kylie Ellis, lead author on the current study explains why new therapies are needed to help victims of stroke: "The reality is, treatment options available to the thousands of stroke patients every year are limited….The primary drug treatment available must be administered within hours of a stroke and many people don't have access within that timeframe, because they often can't seek help for some time after the attack.”

Use of dental pulp stem cells for generation of neurons for brain transplantation would have several advantages. According to Dr Ellis, a major one would be that they can be derived from the patient themselves “for tailor-made brain therapy that doesn't have the host rejection issues commonly associated with cell-based therapies.” Another advantage is that the dental pulp offers an on-going source of stem cells that could be harvested for treatment months or even years after the stroke.

In the current study, the research team investigated the neuronal potential of mouse dental pulp stem cells in an effort to advance the development of a mouse model for neural stem cell transplantation. They developed culturing conditions for mouse dental pulp stem cells that would encourage differentiation of the cells to neurons. On examining the proteins expressed by the cells under these conditions, the researchers found that they expressed biomarkers typical of neurons. In addition, the cells grew in networks resembling those of brain cells. Dr Ellis explains that there is still work to do but that the results are promising: "What we developed wasn't identical to normal neurons, but the new cells shared very similar properties to neurons. They also formed complex networks and communicated through simple electrical activity, like you might see between cells in the developing brain."

The potential of this type of work on dental pulp stem cells is enormous for modelling stroke and other brain disorders and carrying out pre-clinical studies to allow development of revolutionary new treatments and techniques for patients.

Sources:
Ellis, K. et al. (2014). Neurogenic potential of dental pulp stem cells isolated from murine incisors. Stem Cell Research & Therapy 5: 30 doi:10.1186/scrt419

Press release: University of Adelaide; available at http://www.eurekalert.org/pub_releases/2...043014.php [Accessed 1 May 2014].

A new 50-gene cancer panel test launched by the Mayo Clinic is designed to generate “results that oncologists can use to help find the right drug the first time.” That’s according to Dr Benjamin Kipp, a Mayo Clinic molecular geneticist and lead designer of the test. The new test is called CANCP, an abbreviation for Solid Tumor Targeted Cancer Gene Panel by Next-Generation Sequencing.

CANCP is designed to scan ‘hot spots’ of the 50 genes, meaning specific regions of the genes that are known to frequently harbour tumour-causing mutations. Mutations in these 50 genes have been identified as contributing to tumour growth and resistance to chemotherapy. It is specific to solid tumours. The test is aimed at providing a treatment regime tailored to the individual patient. Dr Axel Grothey, a Mayo Clinic oncologist who orders CANCP on selected tumours explains the utility of the test in individualising treatment: “Every patient’s cancer is different, and oncology is moving away from treating cancer based on its location in the body in favour of selecting the best medication for the individual patient based on molecular changes in the tumour….This test helps providers identify such molecular changes without infusing irrelevant details from genes that we know will not affect our choice of medications.”

Currently, CANCP is available to both Mayo Clinic patients and to providers worldwide via Mayo Medical Laboratories. Testing is conducted in the Clinical Laboratory Improvement Amendments (CLIA) -certified Next-Generation Sequencing Lab of the Mayo Clinic Department of Laboratory Medicine and Pathology (DLMP). DLMP and Mayo Medical Laboratories also offer another 17-gene next-generation sequencing panel screening test for hereditary colorectal cancers. Both these tests were developed together with the Mayo Clinic Center for Individualized Medicine.

Sources

Press release: Mayo Clinic; available at http://newsnetwork.mayoclinic.org/discus...panel-test [Accessed 1 May 2014].

http://mayoresearch.mayo.edu/center-for-...d-medicine

In a very intriguing research carried out at the Johns Hopkins University, researchers have unveiled an interesting mode of spreading used by the deadly tumour cells. A propulsion system based on water and charged particles has been introduced, which is proposed to have been used by the tumour cells to spread through extremely narrow three-dimensional spaces in the body. This interesting study marks the need for moving out of the boundaries of the 2D cell-culture studies carried out in controlled conditions of petridishes! Following is a graphical abstract of the concept:

(courtesy: http://www.sciencedaily.com)

Till date, it has been believed (through the 2D petridish based studies), that the cancer cells need actin and other proteins to grip and crawl through the flat surfaces. This has infact been considered the basis of metastasis (spread of tumour systemically) till date. Image below summarizes the mentioned concept:
Thus, deactivation of these actin grips was considered one of the probable ways to curb the spread of the disease, untill in 2012, when Dr. Konstantinos Konstantopoulos (chair person of the Department of Chemical and Biomolecular Engineering, John Hopkins) made the astonishing discovery that cancer cells could move through narrow spaces even without the need of actin filaments or other proteins. That finding ultimately led to further study to decipher the mechanism behind that movement, and which came to fruit with the recent publication in the April 24 issue of the journal Cell.

The tests were carried out in a lab-on-a-chip microfluidic device with state of art imaging techniques, which lead to the development of the Osmotic Engine Model that propels the cancer cells through the tight spaces even without the need of actin filaments. The Osmotic engine is actually a combination of sodium-hydrogen ions, cell membrane proteins called aquaporins, and water. Acting more or less like a Sailboat, tumour cells tend to generate a flow of liquid that takes in water and ions at a cell's leading edge and pumps them out the trailing edge, propelling the cell forward (refer image above).

The Osmotic Model thus highlights following points (as suggested in the article):
1. Actin-independent Movement
2. Polarized distribution of Na+/H+ pumps and aquaporins in confined regions leading to propulsion mechanism
3. Dependency of speed and movement on osmotic conditions of the growth region.
4. Water permeation can thus drive movement through narrow channels

The new biochemical model thus gives us a reason to look into the wider and different aspects of cancer growth. And, infact it reasons as to why some forms of cancer dont respond to a common treatment mode. Whereas this research is in quite an infant stage, the future does seem fruitful and productive in fighting the deadly disease of cancer.

About the source:
The article has been published in the latest issue of the Cell, and titled as "Water Permeation Drives Tumor Cell Migration in Confined Microenvironments"
Authors: Kimberly M. Stroka, Hongyuan Jiang, Shih-Hsun Chen, Ziqiu Tong, Denis Wirtz, Sean X. Sun, Konstantinos Konstantopoulos

Link to abstract: http://www.cell.com/cell/abstract/S0092-...%2900340-7

Courtesy: http://www.sciencedaily.com (For the first report on this article)

It has been recognised for some time that increased intake of dietary fibre can help in weight loss, however the mechanism has remained poorly understood. A new study from research teams in the UK and Spain may have solved the mystery. The study shows that when fibre is fermented by the microbes in the colon a molecule called acetate is released. Acetate is then transported to the brain where it acts as an appetite suppressor. The study is published in the journal Nature Communications.

Obesity has become one of the most serious public health issues facing westernised societies. This new study provides proof of the mechanism behind the effectiveness of including more fibre in our diets to help suppress appetite and thus avoid over-eating. Fruit and vegetables are high in dietary but usually at low levels in processed food. When we digest fibre, it is fermented by microbes in our colon resulting in production of acetate as a waste product.

In the current study, the research team used a form of dietary fibre called inulin which is found, for example, in chicory and sugar beets and is also added to some cereal bars. They used a mouse model, which were fed a high fat diet either with or without added inulin. The mice who had inulin added to their diet ate less and gained less weight than mice with no inulin in their diet. The mice with the inulin-containing diet also had a high level of acetate in their guts.

The researchers used inulin labelled with 13C and traced the 13C-labelled acetate derived from this fibre throughout the body using PET-CT scanning. The labelled acetate was observed to cross the blood-brain barrier. It targeted the hypothalamus region of the brain, which is involved in control of hunger and appetite. The researchers further investigated acetate metabolism in the hypothalamus with a new cutting-edge scanning method called High Resolution Magic Angle Spinning (HR-MAS). Study co-author Professor Sebastian Cerdán explained: "From this we could clearly see that the acetate accumulates in the hypothalamus after fibre has been digested. The acetate then triggers a series of chemical events in the hypothalamus leading to the firing of pro-opiomelanocortin (POMPC) neurons, which are known to supress appetite."

Lead author on the study, Professor Gary Frost explained the implications of these findings for approaching obesity, diet and over-eating: "The average diet in Europe today contains about 15 g of fibre per day…..In stone-age times we ate about 100g per day but now we favour low-fibre ready-made meals over vegetables, pulses and other sources of fibre. Unfortunately our digestive system has not yet evolved to deal with this modern diet and this mismatch contributes to the current obesity epidemic. Our research has shown that the release of acetate is central to how fibre supresses our appetite and this could help scientists to tackle overeating."

This study is the first to show that acetate from dietary fibre affects appetite responses in the brain. Similar effects on amount of food consumed and weight gain in mice were obtained if acetate was directly injected into the bloodstream, colon or brain. Professor Frost explained the challenges inherent in applying these findings to tackling obesity and over-eating: "The major challenge is to develop an approach that will deliver the amount of acetate needed to supress appetite but in a form that is acceptable and safe for humans. Acetate is only active for a short amount of time in the body so if we focussed on a purely acetate-based product we would need to find a way to drip-feed it and mimic its slow release in the gut. Another option is to focus on the fibre and manipulate it so that it produces more acetate than normal and less fibre is needed to have the same effect, providing a more palatable and comfortable option than massively increasing the amount of fibre in our diet. Developing these approaches will be difficult but it's a good challenge to have and we're looking forward to researching possible ways of using acetate to address health issues around weight gain."

Professor David Lomas, Chair of the MRC's Population and Systems Medicine Board, added: "It's becoming increasingly clear that the interaction between the gut and the brain plays a key role in controlling how much food we eat. Being able to influence this relationship, for example using acetate to suppress appetite, may in future lead to new, non-surgical treatments for obesity."

Sources:

G. Frost et al. (2014). The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism, Nature Communications (2014), doi: 10.1038/n-comms4611

Press release: Imperial College London; available from http://www.eurekalert.org/pub_releases/2...043014.php

Scientists from the University of New South Wales in Australia have developed a tiny new ‘lab-on-a-chip’ device with potential applications that include screening of biological molecules, toxic gas detection and integrated circuit fabrication. In the study, published in the journal Nature Communications, the researchers solve the issue of solvent volatility, which has been a problem in making miniaturised devices, by using ionic liquids.

Lab-on-a-chip and miniaturised systems have recently become very popular with their potential for faster reaction times, minimal use of materials and relatively high yields. However, they face problems in terms of lack of reproducibility in some cases and with solvent volatility. Dr Chuan Zhao, senior author of the study, explains how the research team addressed this issue of solvent volatility: "We use a class of 'green' solvents called ionic liquids, which are salts that are liquid at room temperature. They are non-volatile, so this overcomes one of the main problems in making useful miniaturised devices - rapid evaporation of the solvents on the chip." Dr Zhao further explains the potential functions for this device: “The versatility of our chips means they could have a wide range of prospective functions, such as for use in fast and accurate hand-held sensors for environmental monitoring, medical diagnosis and process control in manufacturing."

Other researchers have attempted to address the problem of solvent volatility by confining solvents within walls or channels or using reservoirs for storage of extra solvent on the chip. However, in the current study the researchers used a process called microcontact printing to create a microarray of ionic solvent droplets which were chemically attached to the chip. Each droplet was about 50 micrometres wide- this is about half the width of a human hair- and 10 micrometres long. Dr Zhao explained the practicality of the devices for use in a variety of commercial applications: "These microarray chips can be easily produced in high numbers and are very stable. They can survive being turned upside down and heated to 50 degrees and some can even survive being immersed in another liquid. These properties will be important for commercial applications, including storage and transportation of microchips."

The research team demonstrated the utility of their system in processes including use as substrates for protein immobilisation, high-performance gas sensor arrays or electrochemical cells and reactors for metal microfabrication.

Sources
Gunawan, C.A., Ge, M. and Zhao, C. (2014) Nature Communications 5(3744); doi:10.1038/ncomms4744

Press release: University of New South Wales; available from http://www.eurekalert.org/pub_releases/2...042914.php

In a new study scientists have grown human epidermal equivalents, with skin barrier and cellular properties similar to normal skin, from stem cells. The innovation offers the potential for a cost-effective alternative to animals, both for studying skin barrier defects and for drug and cosmetic screening. The study is published in the journal Stem Cell Reports.

The skin provides a permeability barrier between us and our environment. The outermost layer is called the epidermis and protects us from entry of pathogens as well as retaining moisture. Some skin diseases such as atopic dermatitis are caused by defects in genes in cells called keratinoctyes, from which the cells of the epidermis are derived.

Previously, scientists had been able to generate human epidermal equivalents, which are 3D in vitro models for skin cells. However, use of these human epidermal equivalents was limited by the fact that they did not form a functional permeable barrier. Furthermore, they could only be generated in limited numbers from single samples of epidermis. The current study turned to human embryonic stem cells and induced pluripotent stem cells to generate a population of keratinocytes whose genetic signature was very similar to that of normal human keratinocytes. The researchers then used these engineered keratinocytes in a closely controlled procedure involving sequential high-to-low humidity and an air-liquid interface culture. In this way, they were able to generate an unlimited number of human epidermal equivalents which had the cellular strata of human epidermis and crucially also formed a functional barrier with similar properties to normal skin.

Authors on the study are confident about the utility of their new model for study of skin diseases and testing of drugs and cosmetics. Lead author Dr Dusko Ilic said: “This is a new and suitable model that can be used for testing new drugs and cosmetics and can replace animal models” while co-author Dr Theodora Mauro explained: "We can use this model to study how the skin barrier develops normally, how the barrier is impaired in different diseases and how we can stimulate its repair and recovery."

Sources:

Petrova, A. et al. (2014). 3D In Vitro Model of a Functional Epidermal Permeability Barrier from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells. Stem Cell Reports, http://dx.doi.org/10.1016/j.stemcr.2014.03.009

Press release: King’s College London; Stem Cell Reports

Question by Chikki Renu:

i just now completed my intermediate 2nd year,and wanted to do biotechhnology so which way should i choose degree or engineering?

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Dear Renu,
This is an important decision of your career. So, before you opt for any Major Degree/Course, first set out your career goals. Donot opt for any degree/course blindly. Please answer some of my questions so that I may help you out in whatever capacity I have for the same:

1. Your specialization (major subjects) in intermediate?
2. Any competitive exam applied by you?
3. Your financial condition (how important is it for you to grab a job immediately)
4. Are you interested in long term research?
5. Your academic performance in intermediate.

It's important for me to know answer to these root questions before shedding any blunt advice.

Best wishes

Sunil

A novel DNA vaccine that targets the vasculature (blood vessels) that keep tumours supplied with blood has shown promising results in mouse tumour models. The study, from researchers in the University of Pennsylvania in the USA and the University of Perugia in Italy, is published in the Journal of Clinical Investigation.

Angiogenesis is the name for the process of growth of new blood vessels from pre-existing vessels. It is an essential process in normal processes such as pregnancy, embryonic development, and wound healing. Tumour angiogenesis is a promising target for cancer therapy but previous strategies have encountered problems of specificity as processes such as wound healing were also affected. The current study identified a protein called tumour endothelial marker 1 (TEM1) as a promising target as it is overexpressed in the vasculature many tumours in both humans and mice but is expressed at low or undetectable levels in normal tissues. TEM1 is implicated in tumour vascular cell adhesion, migration and development as well as tumour progression. Its overexpression is linked to poor survival.
In the current study, the research team designed a vaccine in which Tem1 cDNA (which encodes TEM1 protein) was fused to a fragment of tetanus toxin (TT) as adjuvant in a DNA vehicle called a plasmid. This generated the Tem1-TT vaccine. The researchers tested Tem1-TT vaccine by both prophylactic and therapeutic vaccine approaches in mouse models of cancer.

In the prophylactic approach, mice were first inoculated with Tem1-TT vaccine three times at weekly intervals before being subjected to tumour challenge. The results showed that there was significant tumour protection when compared with plasmid carrying only single Tem1 or TT separately. In the therapeutic approach, the mice were first subjected to tumour challenge and then were given 3 weekly vaccinations after 3-5 days. In this case, the vascularity, or blood vessel growth, of tumours was reduced, there was increased infiltration of anti-tumour CD3+ T cells into the tumour and progression of established tumours was controlled. Importantly, the researchers established that effective Tem1-TT vaccination did not affect normal processes such as wound healing and reproduction.

In a bonus anti-tumour effect, the researchers showed that after killing the endothelial cells of the tumour vasculature, a process called epitope spreading resulted. Killing of the endothelial cells created a rich source of dead or dying tumour cells capable of inducing a cross-priming event from mouse immune cells against tumour antigens other than TEM. This process increased the therapeutic efficacy of the vaccine.

Senior author Dr Andrea Facciabene explains how this study potentially advances the field of cancer vaccines: "Until now there have been a lot of clinical trials using DNA vaccines to target tumours themselves, but unfortunately the results have been disappointing…This is a different approach which should heighten optimism for cancer vaccines in general. Moreover, based on what we’ve seen in our mouse studies, this vaccine doesn’t seem to show any significant side effects."

The authors are hopeful that targeting TEM1 will have efficacy as both a prophylactic defence against cancer and to complement therapies such as radiotherapy and chemotherapy. Dr Facciabene explains "Using this vaccine simultaneously with radiation may eventually have a double synergy…Both treatments affect the tumor endothelium, radiotherapy could help the phenomenon of epitope spreading induced by the TEM1-TT vaccine."

Future plans are to continue pre-clinical work with human TEM1 and to move on to Phase I human clinical trials.

Sources:

Facciponte, J.G., Ugel, S., De Sanctis, F., Li, C., Wang, L., Nair, G., Sehgal, S., Raj, A., Matthaiou, E., Coukos, G. and Facciabene, A. Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature. J. Clin. Invest. 2014; 124(4):1497–1511 doi:10.1172/JCI67382

Press release: University of Pennsylvania School of Medicine; available at http://www.uphs.upenn.edu/news/News_Rele...acciabene/

If you are keenly interested in the domain of Membrane Transport and Different drug-delivery systems, then Roche's "Nature Biotechnology Symposium 2014: Unlocking Cell Transport Barriers to Deliver Large Molecule Therapeutics". is a must attend!

The symposium is aimed at bringing together the scientific community (especially the cell-biologists and drug-delivery experts) to understand the intricacies and developments in membrane biology that may be exploited to efficate the current drug distribution, cellular uptake and delivery systems.

Importantly: It's a FREE event.
( attendees will be selected to participate on the basis of their application for admission)



Application and abstract submission deadine: June 16, 2014

Venue: Roche Forum Buonas, Buonas, Switzerland

September 3-5, 2014

APPLY HERE

A new drug targeting angiogenesis- new blood vessel growth- of tumours has just received approval from the U.S. Food and Drug Administration (FDA) as a second line treatment for stomach cancer after initial chemotherapy has been unsuccessful. The generic name for the drug is ramucirumab. It is a monoclonal antibody directed against the vascular endothelial growth factor (VEGF) receptor-2 on blood vessel cells. It has been approved based on the results of a clinical trial carried out by scientists in Dana-Farber Cancer Institute and the approval was announced by the manufacturers, Lilly Oncology, of Indianapolis. It will be sold under the name Cyramza.

Advanced stomach cancer is notoriously difficult to treat effectively. In 2014 an estimated 22,290 people will be diagnosed with stomach cancer in 2014; 10,990 of them will die of the disease. This is the first FDA-approved treatment for this form of cancer.

The clinical trial on which the approval was based was called REGARD and was led by Dr Charles Fuchs, director of the Gastrointestinal Cancer Center at Dana-Farber. The patients enrolled in the study had advanced or metastatic gastric cancer – cancer of the stomach – or cancer at the junction of the oesophagus with the upper part of the stomach. Their cancer had progressed in spite of initial chemotherapy treatment.

The results of the trial showed that use of ramucirumab induced improvement in survival and a reduced rate of cancer progression compared to placebo. The median overall survival of patients with advanced stomach was increased modestly by 37%, to 5.2 months compared to 3.8 months for patients on placebo. They also had a 62% increase in survival time before the cancer progressed, at 2.1 months compared to 1.3 months for placebo. The modest nature of the improvements has led some commentators to question whether ramucirumab effects are really meaningful or just marginal. Dr Fuchs explains: "The benefit is modest, but it's clearly better than what we were previously doing…. when you chip away and develop drugs in sequence, ultimately you do have meaningful clinical improvements."

Another randomised clinical trial on ramucirumab, called the RAINBOW trial, examined use of ramucirumab in combination with paclitaxel in patients with advanced stomach or gastroesophageal junction cancer. The combination prolonged overall survival from a median of 7.36 months to 9.63 months. The current FDA approval of ramucirumab does not extend to combination therapy, but Lilly Oncology plans to submit the RAINBOW data in order to seek expanded approval. These results have increased confidence that the effects of ramucirumab may be more than marginal.

Dr Fuchs concludes: "For years we have looked for new and really effective drugs for stomach cancer….We have relied on standard chemotherapies for a long time, and we've needed targeted agents based on the fundamental biology of stomach cancer."

Sources:

Press release: Dana-Farber Cancer Institute; available from http://www.eurekalert.org/pub_releases/2...042114.php

Wadhwa, R., Elimova, E., Shiozaki, H., Sudo, K., Blum, M.A., Estrella, J.S., Chen, Q., Song, S. & Ajani, J.A. 2014, "Anti-angiogenic agent ramucirumab: meaningful or marginal?", Expert Review of Anticancer Therapy, vol. 14, no. 4, pp. 367-379.

Shah, M.A. 2014, "Gastrointestinal cancer: targeted therapies in gastric cancer-the dawn of a new era", Nature Reviews.Clinical oncology, vol. 11, no. 1, pp. 10-11.

The CRISPR-Cas9 nucleases are increasingly commonly used genome editing tools with potential for future therapeutic application. However, the monomeric versions up to use until now are prone to processing errors in which they produce unwanted off-target mutations at a significant rate, making it inappropriate for use in a clinical setting. A new study from researchers in Massachusetts General Hospital describes an important modification of this system what substantially improves the precision. The paper is published online in the journal Nature Biotechnology.

The CRISPR-Cas9 nucleases combine a short RNA segment that matches a relevant DNA target with Cas9, a DNA-cutting enzyme. They were initially developed in 2012 and are easier to use than earlier genome editing systems such as ZFN (zinc finger nuclease) and TALEN (transcription activator-like effector nuclease) systems. They have been used in animal models and human cells to induce genomic changes. However, previous reports from the laboratory where the current study was carried out had shown that CRISPR-Cas nucleases produced additional mutations in human cells at high frequency, even at sites differing from the intended DNA target by as many as five nucleotides.

In the current study, the targeting activity of Cas9 was fused to a nuclease called FokI. FokI only cuts when two guide RNAs are bound to the DNA within a strictly defined distance and orientation, a process known as dimerization. Thus the new nucleases were termed dimeric RNA-guided FokI nucleases (RFNs). The need for dimerization effectively doubled the length of DNA that must be recognized for cleavage by RFNs. This significantly improved precision of genome editing without any sacrifice of on-target modification effectiveness.

Senior author Dr J. Keith Joung explained the importance of this modification for future therapeutic applications that require high precision in genome editing: "This system combines the ease of use of the widely adopted CRISPR/Cas system with a dimerization-dependent nuclease activity that confers higher specificity of action…..Higher specificity will be essential for any future clinical use of these nucleases, and the new class of proteins we describe could provide an important option for therapeutic genome editing." The researchers have also developed a software application that will help users identify potential RFN target sites. They have incorporated it into the freely available software package ZiFiT Targeter, which can be accessed at http://zifit.partners.org.

Sources:

Tsai, S.Q., Wyvekens, N., Khayter, C., Foden, J.A., Thapar, V., Reyon, D., Goodwin, M.J., Aryee, M.J. and Joung, J.K. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nature Biotechnology (2014); doi:10.1038/nbt.2908

Press release: Massachusetts General Hospital; available at http://www.eurekalert.org/pub_releases/2...042514.php

Dear All
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Does the reputation of the Pharma/Biotech company that you work for matter when you apply for another position in the sciences or quality departments? Specifically, if you work for a company that doesn't have a great reputation, will that hurt your chances of getting hired elsewhere?

I have been offered a position (no other offers yet) and am wondering if, because I just graduated and this is my first industry position, working for a company with a not so stellar reputation will kill my chances of being hired at other companies in the years to come?

Thank you.

Hello guys,

I would like to know if, with all things being equal, a Biotechnology degree is the same as a degree in Biology: Concentration in Biotechnology? Unfortunately, my university only offers this degree and I am stump on what to do with it once I graduate. I recently switch from Biochemistry to Bio: Conc. Biotech so I am completely clueless. I am worried about what career I can make out of this if I don't decide to go to a med or even a grad school. Thanks a lot!

HELLO,

please share your knoweledge regarding carrer prospects for those who have done m.sc biotechnology in India and wanna start carrer in usa . it can be ph.d or any job oriented course and then job in any biotechnology form in usa.
please guide.. what is the procedure, what is the eligibility crieteria, importat dates/ month for application , short term study so tht you can work there?

thanks

A new study confirms that apart from the discovery of new knowledge and the long-term impact of such knowledge, scientific research also contributes to short-term economic gain. The study, published in this week’s Science journal, is the first of its kind to generate large-scale systematic data on short-term effects of science funding. The study was carried out by researchers from the American Institute of Research, the Committee on Institutional Cooperation, University of Michigan, University of Chicago, and the Ohio State University using data from the STAR METRICS project. This is a partnership between federal science agencies and research institutions set up to document the return to the public of science investments.

Policy-makers have an interest in the evidence of the short-term economic value of science-funding. The new study was carried out to document this in the United States. It focused on nine universities including Michigan, Wisconsin-Madison, Minnesota, Ohio State, Northwestern, Purdue, Michigan State, Chicago and Indiana. These universities were awarded approximately $7 billion in research and development funding in 2012 of which approximately 56% was from federal government. The study results shed light both on composition of the scientific workforce in these universities and the national impact of science research on businesses that supply laboratories funded by federal grants.

The study found that most people employed under federal research funding are not faculty members; in fact less than 20% are faculty researchers. The remainder is made up from graduate and undergraduate students, research staff, staff scientist and post-doctoral fellows. The researchers were also able to ascertain that each university receiving federal funding spent it in widely throughout the United States, with approximately 70% being spent outside their home states. While a large proportion of funding went to big companies, small enterprises also benefitted. In analysing the spending patterns, the researchers commented that "we were struck by how many are small, niche, high-technology companies…"

Co-author Roy Weiss, Deputy Provost for Research at the University of Chicago, said, "Research universities are dedicated to the discovery of new knowledge. This study reports the first cooperative endeavour by multiple universities to evaluate the benefit of government investment in research. In addition to making the world a better place by virtue of these discoveries, we now have data to support the overall benefits to society."

Julia Lane, Senior Managing Economist at the American Institutes for Research and a lead researcher on the project, further summarised, "This study provides evidence that while science is complicated, it is not magic. It is productive work. Scientific endeavours employ people. They use capital inputs. Related economic activity occurs immediately. Policy makers need to have an understanding of how science is produced when making resource allocation decisions, and this study provides that information in a reliable and current fashion."

Sources:

Weinberg, B.A., Owen-Smith, J., Rosen, R.F., Schwarz, L., McFadden Allen, B., Weiss, R.E. and Lane, J. (2014). Science Funding and Short-Term Economic Activity. Science, 4 April 2014, 344(6179), 41-43; DOI: 10.1126/science.1250055

Press release: Committee on Institutional Cooperation; available from http://www.eurekalert.org/pub_releases/2...033114.php

Defects in motor neurons lead to the devastating motor neuron diseases of which the most common human form is amyotrophic lateral sclerosis (ALS). A new study from scientists in the University of Wisconsin-Madison has identified a defect in production of the protein neurofilament-L (NF-L) as the cause of neurofilament tangles in the nerve fibres. These tangles interfere with transmission of signals to muscles, resulting in muscle paralysis. The study was published online on April 3 in the journal Cell Stem Cell.

In ALS, essential voluntary muscle activity such as speaking, walking, breathing, and swallowing is adversely affected. The disease causes paralysis and death. Motor neurons control muscles under normal circumstances, but in ALS, motor neurons lose the ability to relay signals from the brain to the muscles. It was recently discovered that a mutation in the Cu/Zn superoxide dismutase (SOD1) gene was present in some ALS patients.

Attempts by researchers to transfer the mutated gene to animals and identify drugs to treat those animals were not yielding useful results. The current study adopted a more fundamental approach by using induced pluripotent stem cells (iPSCs) from patients with the SOD1 mutation. This was achieved using skin cells from patients that were transformed into induced pluripotent stem cells and in turn, into motor neurons. These iPSCs can be used as "disease models," as they carry many of the same traits as their donor. Dr Su-Chun Zhang, senior author on the paper, explains that this approach had an advantage of the genetic approach which "can only study the results of a known disease-causing gene. With iPSC, you can take a cell from any patient, and grow up motor neurons that have ALS. That offers a new way to look at the basic disease pathology."

Using this approach, the research team identified neurofilament, a structure that transports chemicals and cellular subunits including neurotransmitters to the far reaches of the nerve cell, for example signalling the muscles to move. In particular, mutant SOD1 caused decreases in stability of the messenger RNA encoding NF-L and hence reduction in the proportion of NF-L in neurofilament. This in turn resulted ibn neurofilament aggregation and formation of tangles. These tangles block the nerve fibres, so that they malfunction and die.
This discovery may have far-reaching consequences beyond ALS. Dr Zhang explains: "Our discovery here is that the disease ALS is caused by misregulation of one step in the production of the neurofilament," but "very similar tangles" appear in Alzheimer's and Parkinson's diseases. "We got really excited at the idea that when you study ALS, you may be looking at the root of many neurodegenerative disorders."

The misregulation occurs very early in motor neuron development, making it the most likely cause of this disease. When the research team edited NF-L expression in the SOD1-mutant motor neurons, cells were returned to normal. Dr Zhang reports that scientists at the Small Molecule Screening and Synthesis Facility at UW-Madison are searching for ways to rescue the defective motor neurons by testing libraries of candidate drugs. He concludes: "This is exciting. We can put this into action right away. The basic research is now starting to pay off. With a disease like this, there is no time to waste."

Sources

Chen, H. et al. (2014) Modeling ALS with iPSCs Reveals that Mutant SOD1 Misregulates Neurofilament Balance in Motor Neurons. Cell Stem Cell, April 3rd; DOI: http://dx.doi.org/10.1016/j.stem.2014.02.004

Press release: University of Wisconsin-Madison; available at http://www.eurekalert.org/pub_releases/2...040114.php

The liver is a major cause of late-stage failure of new drugs due to toxicity reactions in humans that are not detected in animals. There is currently a lack of adequate in vitro liver tissue models that could be used to help overcome this limitation. However, a new study from researchers from the Center for Engineering in Medicine at the Massachusetts General Hospital has taken a step forward. The researchers used a novel ultrathin collagen matrix assembly which maintained liver cells in a fully functional and differentiated form. The study is published in the current issue of the journal Technology.

This microscale ‘organ-on-a-chip’ device is a prime example of 3-D microtissue biotechnological engineering. The use of collagen, a biologically relevant extracellular matrix molecule, allows liver cells to be provided with the correct extracellular matrix cues to maintain their morphology and This provides an in vitro tool for re-creating liver micro-tissues by layering together all the different liver cell types. This would facilitate study of healthy liver physiology and liver diseases. Importantly, new and experimental drug liver toxicity could be dissected before moving to animals or the clinic.

Senior author Dr Martin Yarmush explains: "This is a clever combination of the well-known layer-by-layer deposition technique for creating thin matrix assemblies and collagen functionalization chemistries that will really enable complex liver microtissue engineering by replicating the physiological cues that maintain the state of liver cell differentiation….The ultrathin collagen matrix biomaterial and its ability to keep liver cells functional for longer periods of time in chip devices will undoubtedly be a useful tool for creating liver microtissues that mimic the true physiology of the liver, including cell and matrix spatial geometries".

Sources:

McCarty, W.J., Usta, O.B., Luitje, M., Sundhar Bale, S., Bhushan, A., Hegde, M., Golberg, I., Jindal, R. and Yarmush, M.L. (2014). A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering: Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte culture. Technology 02, 67 (2014). DOI: 10.1142/S2339547814500083.

Press release: World Scientific; available at http://www.worldscientific.com/page/pres...4-04-02-07 [Accessed 4 April 2014].

Accompanying figure: “An ultrathin collagen matrix assembly maintained the morphology and function of primary liver hepatocytes in a microfluidic organ-on-a-chip device for two weeks. Three images of the hepatocytes after two weeks in a microfluidic device: A phase contrast image of cell morphology at two weeks showing dense cytoplasm, distinct nuclei, and bright cell borders; bile canalicular network development (red); and cell nuclei (blue) and actin (green) organization demonstrating cell polarity.” Credit: William McCarty, the Center for Engineering in Medicine at the Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children-Boston).

"Optogenetics" allow researchers to stimulate synaptic activity in specific neurons that are made to express light-sensitive ion channels (channelrhodopsins). Despite the variety of opsins with different peak wavelength sensitivities, until now it has not been possible to independently activate two distinct neural populations without significant cross-talk or losing temporal resolution. Researchers at MIT reported in Nature on two new opsins with non-overlapping excitation spectra, Chronos and Chrimson, that allow independent optical excitation of distinct neural populations in mouse brain slices. These tools open the door to explore how multiple synaptic pathways interact to encode information in the brain.

Opsin genes occur naturally in microbial algae. In order to efficiently express these genes in mammalian cells, these researchers turned to GenScript for codon optimization and gene synthesis. GenScript has developed the leading codon-optimization algorithm:

OptimumGene?, patented in 2012 and continuously improved based upon the latest research findings.

Two new opsins with non-overlapping excitation spectra, Chronos and Chrimson, that allow independent optical excitation of distinct neural populations