Tuesday, October 21, 2014

Bioinformatics approach helps Researchers find new use for Old drug

Developing and testing a new anti-cancer drug can cost billions of dollars and take many years of research. Finding an effective anti-cancer medication from the pool of drugs already approved for the treatment of other medical conditions could cut a considerable amount of time and money from the process. Now, using a novel bioinformatics approach, a team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has found that the approved antimicrobial drug pentamidine may help in the treatment of patients with advanced kidney cancer. Described online in the journal Molecular Cancer Therapeutics, the discovery reveals how linking cancer gene expression patterns with drug activity might help advance cancer care.

"The strategy of repurposing drugs that are currently being used for other indications is of significant interest to the medical community as well as the pharmaceutical and biotech industries," says senior author Towia Libermann, PhD, Director of the Genomics, Proteomics, Bioinformatics and Systems Biology Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. "Our results demonstrate that bioinformatics approaches involving the analysis and matching of cancer and drug gene signatures can indeed help us identify new candidate cancer therapeutics."
Renal cell cancer consists of multiple subtypes that are likely caused by different genetic mutations. Over the years, Libermann has been working to identify new disease markers and therapeutic targets through gene expression signatures of renal cell cancer that distinguish these different cancer subtypes from each other, as well as from healthy individuals. In this paper, he and his colleagues were looking for drugs that might be effective against clear cell renal cancer, the most common and highly malignant subtype of kidney cancer. Although patients with early stage disease can often be successfully treated through surgery, up to 30 percent of patients with renal cell cancer present with advanced stages of disease at the time of their diagnosis.
To pursue this search, they made use of the Connectivity Map (C-MAP) database (http://www.broadinstitute.org/cmap), a collection of gene expression data from human cancer cells treated with hundreds of small molecule drugs.
"C-MAP uses pattern-matching algorithms to enable investigators to make connections between drugs, genes and diseases through common, but inverse, changes in gene expression," says Libermann. "It provided us with an exciting opportunity to use our renal cell cancer gene signatures and a new bioinformatics strategy to match kidney cancer gene expression profiles from individual patients with gene expression changes inducted by various commonly used drugs."
After identifying drugs that may reverse the gene expression changes associated with renal cell cancer, the investigators used assays to measure the effect of the selected drugs on cells. This led to the identification of a small number of FDA-approved drugs that induced cell death in multiple kidney cancer cell lines. The investigators then tested three of these drugs in an animal model of renal cell cancer and demonstrated that the antimicrobial agent pentamidine (primarily used for the treatment of pneumonia) reduced tumor growth and enhanced survival. Gene expression experiments using microarrays also identified the genes in renal cell cancer that were counteracted by pentamidine.

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Bioinformatics Department

Tuesday, September 30, 2014

Human genome was shaped by an evolutionary arms race with itself

New findings suggest that an evolutionary arms race between rival elements within the genomes of primates drove the evolution of complex regulatory networks that orchestrate the activity of genes in every cell of our bodies.
The arms race is between mobile DNA sequences known as "retrotransposons" (a.k.a. "jumping genes") and the genes that have evolved to control them. The identified genes in humans that make repressor proteins to shut down specific jumping genes. The researchers also traced the rapid evolution of the repressor genes in the primate lineage.
The primate genomes have undergone repeated episodes in which mutations in jumping genes allowed them to escape repression, which drove the evolution of new repressor genes, and so on. The findings suggest that repressor genes that originally evolved to shut down jumping genes have since come to play other regulatory roles in the genome.
Retrotransposons are thought to be remnants of ancient viruses that infected early animals and inserted their genes into the genome long before humans evolved. Now they can only replicate themselves within the genome. Depending on where a new copy gets inserted into the genome, a jumping event can disrupt normal genes and cause disease. Often the effect is neutral, simply adding to the overall size of the genome. Very rarely the effect might be advantageous, because the added DNA can itself be a source of new regulatory elements that enhance gene expression. But the high probability of deleterious effects means natural selection favors the evolution of mechanisms to prevent jumping events.
The jumping genes or "transposable elements" account for at least 50 percent of the human Genome and retrotransposons are by far the most common types. The expansion of this family of repressor genes occurred in response to waves of retrotransposon activity. Because repression of a jumping gene also affects genes located near it on the chromosome, the researchers suspect that these repressors have been co-opted for other gene-regulatory functions, and that those other functions have persisted and evolved long after the jumping genes the repressors originally turned off have degraded due to the accumulation of random mutations.
"The way this type of repressor works, part of it binds to a specific DNA sequence and part of it binds other proteins to recruit a whole complex of proteins that creates a repressive landscape in the genome. The idea that they are involved in repression of jumping genes is not new, previous studies by other researchers have shown that these proteins silence jumping genes in mouse embryonic stem cells. But until now, no one had been able to demonstrate that the same thing occurs in human cells.
The results demonstrated that two human proteins called ZNF91 and ZNF93 bind and repress two major classes of retrotransposons (known as SVA and L1PA) that are currently or recently active in primates. Analysis of primate genomes, including the reconstruction of ancestral genomes, which showed that ZNF91 underwent structural changes 8 to 12 million years ago that enabled it to repress SVA elements.

Experiments with ZNF 93, which shuts down L1PA retrotransposons, provided a striking illustration of the arms race between jumping genes and repressors. The researchers found that, while it is good at shutting down many L1PA elements, there is one subset of a recently evolved lineage of L1PA that has lost a short section of DNA that includes the ZNF93 binding site. Without the binding site, these jumping genes evade repression by ZNF93. Interestingly, when the researchers put the missing sequence back into one of these genes and put it in a mouse cell without ZNF93, they found that it was better at jumping. So even though the sequence helps with jumping activity, losing it gives the jumping gene an advantage in primates by allowing it to escape repression by ZNF93.

Monday, September 8, 2014

Advancements in Biotechnology

Biotechnology as the name indicates is the assemblage of technology in science of biology. Modern Biotechnology initiated with the discovery of double helical structure of the DNA. Subsequent investigation that helped in unraveling the process of inheritance pattern provided impetus to biotechnological research. It plays a key role in various areas, such as functional genomics, structural genomics, and proteomics. It soon becomes evident that by the use of suitable plasmid and bacteriophage vectors that transformation and transduction of foreign genes into heterologous hosts could be achieved. This led to the production of therapeutic proteins, transgenic plants and development of many novel vaccines. ­­There are many applications of Biotechnology such as development of various medicines, vaccines, increase of productivity, conservation and animal breeding, improvement of quality of seeds, insecticides and fertilizers.

Career in biotechnology: Biotechnologist can work in pharmaceutical companies, chemical, agriculture and allied industries, bio-processing industries, research laboratories run by the government as well as the corporate sector. Bioinformatics, an application of biotech and an interdisciplinary field that solves biological problems using computational techniques. When most people think of opportunities for careers in biotechnology, they think of a scientist in a white coat in a laboratory developing drugs to improve the quality of life. However, biotechnology has a wide variety of career opportunities ranging from sales and marketing, to research and development, to manufacturing and quality control and assurance. 

The biotechnology industry continues to flourish nationwide. Not only are the total number of biotechnology companies increasing, but employment in the biotechnology field continues to grow as well. The biotechnology industry is constantly growing; during the past 10 years the number of employees has increased by more than 90 percent! If you enjoy science, math, technology, investigating and solving problems, and making useful products, a career in biotechnology may be for you. Various biotechnology careers include forensic DNA analyst, scientist, clinical research associate job, laboratory assistant, microbiologist, greenhouse and field technician, bioinformatics specialist, animal caretaker and many more.

Biotech Department
BII Noida

“Global Bioinformatics Market: Industry Size, Trends and Forecast 2014-2018”

Global Industry Analysts Inc. (GIA) announces the release of a comprehensive global report on Bioinformatics markets. The global Bioinformatics market is forecast to reach US$6.8 billion by the year 2017. Principal factors driving market growth include significant development in the field of genomics and its ever-growing application in the research and development processes; breakthrough technologies in drug discovery initiatives; and the entry of new market players along with the growth in size and revenues of existing companies. Going forwards, the penetration of genomics in drug discovery is expected to increase further, which bodes tremendous market prospects for bioinformatics.

Research and Development Extent
Backed by significant developments in the area of genomics, there is increase in the overall volume of distinct biological data, which includes protein and gene sequences. This leaves an arduous task for R&D laboratories of analysis. Data management tools based on bioinformatics have helped companies in easing this task, thereby enhancing their productivity by way of identifying new biomarkers for toxicity and drug efficacy, diagnostic biomarkers as well as new drug targets. Bioinformatics help utilization of this gene and protein data and construct interactive models that aid in identifying disease pathways and effects of compounds. The penetration of genomics in drug discovery is expected to witness further growth, which bodes tremendous market prospects for bioinformatics. It is expected that more and more investments would be made by pharmaceutical companies in research and development initiatives, of which a major chunk would be towards bioinformatics. Concerns associated with patent expiries of several blockbuster drugs, shrinking product pipelines, and increasing drug development costs are driving pharma companies to seek help from biotechnology. Bioinformatics, being helpful at every stage of R&D processes in biotechnology and pharmaceutical sectors, offers increasing potential for future growth.
Market Reports Related to Applications in Bioinformatics

The market of bioinformatics report includes market dynamics and trends in order to give a thorough analysis of the overall competitive scenario in the global bioinformatics market. Thus, market overview section of the report demonstrates market dynamics and trends such as the drivers, restraints, and opportunities that influence the current nature and future status of bioinformatics market globally. Impact factors such as market attractiveness analysis (by geography), market share analysis by key players and Porter’s five forces (bargaining power of suppliers, bargaining power of buyers, threat of substitutes, threat of new entrants and competitive rivalry) analysis have also been explained in the market overview section of the report. Further, this report includes average selling price analysis (in terms of USD) and value chain analysis of bioinformatics market.

 The global bioinformatics market is classified on the basis of platforms, tools and services. Platforms segment includes market analysis of sequence manipulation platforms, sequence alignment platforms, sequence analysis platforms and structural analysis platforms. Tools segment includes market analysis of general knowledge management tools and specialized knowledge management tools. Services segment includes market analysis of sequencing services, database and management services, data analysis services and other services. A thorough market analysis and forecast for these segments has been provided in this study, in terms of market revenue (USD million) for the period 2012 to 2020. The report also provides compounded annual growth rate (CAGR %) for each segment type for the forecast period of 2014 to 2020, while market size estimations have been made considering 2013 as the base year.

Further, the global bioinformatics market is classified into application namely, preventive medicine, molecular medicine, gene therapy, drug development and others. The present and future market sizes (in terms of USD million) of the above mentioned application segments have been given in the report for the period of 2012- 2020 along with their compound annual growth rate (CAGR %) for the period 2014 to 2020. The study further provides recommendations which would be useful for the current and future market players to sustain and grow in the global bioinformatics market.

The report further includes market analysis of regional markets namely, North America, Europe, Asia-Pacific, and Rest of the World (RoW). A thorough market analysis and forecast for these regional markets has been provided in this study, in terms of market revenue (USD million) for the period 2012 to 2020. The report also provides the compounded annual growth rate (CAGR %) for each regional market for the forecast period of 2014 to 2020, while market size estimations have been made considering 2013 as the base year. 

Bioinformatics Companies Concern
Bioinformatics globally is a fairly concentrated market characterized by few large companies and several small players. About 55% of the companies are based in the US, while 30% are based in Europe. Major players profiled in the report include 3rd Millennium Inc., Accelrys Inc., Affymetrix Inc., Agilent Technologies, Celera Group, Gene Logic, Geneva Bioinformatics S.A, IBM Life Sciences, ID Business Solutions Ltd., Instem Scientific Limited (Formerly BioWisdom, Ltd.), Life Technologies Corp., Kinexus Bioinformatics Corp., Nonlinear Dynamics Ltd., among others. 

Bioinformatics Department
BII Noida

Thursday, August 21, 2014

How lizards regenerate their tails: Researchers discover genetic 'recipe

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic "recipe" for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.An interdisciplinary team of scientists used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration. The team studied the regenerating tail of the green anole lizard (Anolis carolinensis), which when caught by a predator, can lose its tail and then grow it back.
"Lizards basically share the same toolbox of genes as humans," said lead author Kenro Kusumi, professor in ASU's School of Life Sciences and associate dean in the College of Liberal Arts and Sciences. "Lizards are the most closely-related animals to humans that can regenerate entire appendages. We discovered that they turn on at least 326 genes in specific regions of the regenerating tail, including genes involved in embryonic development, response to hormonal signals and wound healing."
Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the 'Wnt pathway' -- a process that is required to control stem cells in many organs such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.
"Regeneration is not an instant process," said Elizabeth Hutchins, a graduate student in ASU's molecular and cellular biology program and co-author of the paper. "In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail."

"We have identified one type of cell that is important for tissue regeneration," said Jeanne Wilson-Rawls, co-author and associate professor with ASU's School of Life Sciences. "Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues."
"Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail," said Kusumi. "By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future."
The researchers hope their findings will help lead to discoveries of new therapeutic approaches to spinal cord injuries, repairing birth defects, and treating diseases such as arthritis.The research team included Kusumi, Hutchins, Wilson-Rawls, Alan Rawls, and Dale DeNardo from ASU School of Life Sciences, Rebecca Fisher from ASU School of Life Sciences and the University of Arizona College of Medicine Phoenix, Matthew Huentelman from the Translational Genomic Research Institute, and Juli Wade from Michigan State University. This research was funded by grants from the National Institutes of Health and Arizona Biomedical Research Commission.

Keerti Mishra
Faculty Of Biotechnology

Wednesday, August 13, 2014

When Will We Have a Vaccine for Ebola Virus?

The deadly Ebola outbreak in west Africa highlights the urgent need for a vaccine, and researchers say one may be available in a few years

Source: Scientific American
The latest outbreak of Ebola virus in west Africa is the worst ever—as of Monday, it had infected more than 1,200 people and claimed at least 672 victims since this spring. Guinea, Liberia and Sierra Leone all have confirmed cases. An official at Doctors Without Borders has declared the outbreak as “totally out of control,” according to NBC News. Unfortunately, doctors have no effective vaccines or therapies. Health care workers can only attempt to support patients’ immune systems (regulating fluids, oxygen levels, blood pressure and treating other infections) to help the afflicted fight off the virus as best they can.
A vaccine to help battle future Ebola outbreaks may be just a few years away, however. During the past decade researchers have made significant progress, and vaccines have worked in nonhuman primates. But it has been hard to raise money for human safety tests. To learn about the latest advances as well as obstacles, Scientific American spoke to Thomas Geisbert, a virologist in the Department of Microbiology and Immunology at The University of Texas Medical Branch at Galveston. He’s studied the Ebola virus since 1988 and is currently involved in vaccine research and development.

 Are there any promising vaccines in development for the Ebola virus?
There are quite a few preventative vaccines in development, with three to five that have been shown to completely protect nonhuman primates against Ebola. Some of these vaccines require three injections or more and some require just a single injection. Most of them are being funded by the U.S. government, so they’re in various stages of development, but none of them are  licensed.

The hang-up point with these vaccines is the phase I trials in humans. That’s where scientists get frustrated because we know these vaccines protect animals and we don’t quite understand the regulatory process of why things can’t move faster. I can’t give you an answer as to why it’s taking so long.

Why doesn’t the human immune system fight the virus off?
The Ebola virus is usually transmitted by close contact and the first cells it affects are cells important to your primary immune response—monocytes, macrophages and dendritic cells. These cells are important because they’re the first to recognize that something foreign has entered your body and the first cells to trigger your innate immune system to fight off the infection. This makes it hard to mount an effective immune response against the virus—your body has a tough time fighting the virus off, and the virus multiplies to the point that it takes over major organs in your body.
I’ll give you an example of how a vaccine might work. The vaccine VSV is probably one of the most promising, and it’s based on a viral vector related to the rabies virus. It’s a bullet-shaped particle, and on its surface is a structural protein called a “glycoprotein,” which allows a virus to recognize a host cell, bind to it and take over the host cell’s machinery. With a vaccine, we remove the gene that encodes the glycoprotein of the VSV virus and we replace it with a gene that encodes the glycoprotein of Ebola. You end up with a vaccine that has an Ebola glycoprotein on the surface. Now, it doesn’t behave like Ebola because the rest of its genome is not Ebola, but because it has the Ebola glycoprotein your body is going to recognize it as foreign and build up an immune response against Ebola.

How far along in development is the VSV vaccine?
It’s at the point now where we’re trying to get the funds to do the human studies.
What are the biological challenges of developing a vaccine for Ebola?
There are some vaccines that are “replication defective,” meaning they don’t replicate, and they tend to be safer. Then there are other vaccines that are more efficacious, but they’re “replication competent.” An example of the latter would be the measles vaccine or yellow fever vaccine. They’re usually crippled, so they’re not as dangerous as a wild type virus but certain people could have an adverse event when given a vaccine that’s replication competent.

Replication-competent vaccines may only require a single injection whereas with the replication-defective vaccines you might have to get boosters every year, because they’re not as efficient. So do you go for a vaccine that protects humans in a single injection? In Africa you almost have to, because in an area like that you’re lucky to get someone into a clinic to be vaccinated once. It’s a trade-off—efficacy versus safety. That’s one of the biggest challenges.
Can you give an estimate for when we might have an effective Ebola virus vaccine?
My guess is anywhere from two to six years. I hate to say this, but it really depends on financial support for the small companies that develop these vaccines. Human studies are expensive and require a lot of government dollars.
I would like to see a situation where we tried to advance our lead candidate vaccines as fast as we can to get phase I studies done. I think we should start with the first responders—the health care workers in areas of high risk. This outbreak is so unique because it’s occurring in an area we’ve never seen it before and also because it seems there’s a higher percentage of medical staff infected than we’ve seen before. I’ve seen all of these vaccines work in numerous animals and I’ve never seen an adverse event from them. I appreciate the safety concerns but it would be great if there were some way to fast-track this. People are being exposed to Ebola and there’s a 60 to 90 percent chance they’re going to die—I think we have to look at it in this context.
Faculty of Bii

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