Britain to make genome database


DNA molecule

Briton has taken the initiative when it comes to mass sequencing and are doing it in order to provide better health care opportunities to their residents.

Britain will be the first country to introduce a database of genetic sequences into a mainstream health service, officials say, giving doctors a more advanced understanding of a patient’s illness and what drugs and other treatments they need.

It could significantly reduce the number of premature deaths from cancer within a generation, Prime Minister David Cameron’s office said in a statement.

“By unlocking the power of DNA data, the NHS (National Health Service) will lead the global race for better tests, better drugs and above all better care,” Cameron said on Monday.

His government has set aside 100 million pounds ($160 million) for the project in the taxpayer-funded NHS over the next three to five years.

Harpal Kumar, chief executive of the charity Cancer Research UK, said the work would uncover new information from which doctors and scientists will learn about the biology of cancers and develop new ways to prevent, diagnose and treat them.

He said some targeted, or personalized, cancer treatments such as Novartis’ Gleevec, or imatinib – a drug for chronic myeloid leukemia – are already helping to treat patients more effectively.

Some critics of the project, known as the “UK genome plan”, have voiced concerns about how the data will be used and shared with third parties, including with commercial organizations such as drug companies.

Genewatch, a campaign group fighting for genetic science and technologies to be used in the public interest, has said anyone with access to the database could use the genetic codes to identify and track every individual on it and their relatives.

Cameron’s office said the genome sequencing would be entirely voluntary and patients would be able to opt out without affecting their NHS care. It said the data would be made anonymous before it is stored.

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Genetic Revolution and its impact on society: over view


Nobel Week pic

Today, a special webcast was broadcasted globally under the umbrella of Noble Week Dialogue. The webcast was titled Genetic Revolution and its impact on society and consisted of leading scientists and Nobel Laureates too. Noble Week Dialogue is a latest addition to the event pertaining to the run up to the Noble Prize main event.

The goal of the event was to bring together a select group of the world’s leading scientists, policy-makers and thinkers for a series of thought-provoking sessions and working groups on a topical science related theme. The theme for the 2012 Nobel Week Dialogue was The Genetic Revolution and its Impact on Society, a choice partly inspired by the fact that 2012 marks the 50thanniversary of the award of the 1962 Nobel Prize in Physiology or Medicine to Francis Crick, James Watson and Maurice Wilkins for their discovery of the molecular structure of DNA.

After introductory remarks, Eric Lander, esteemed scientists spoke on  Five Turns of the Double Helix, followed by an on stage interview with James Watson by Matt Ridley. Then Helga Nowotny spoke on  A Social Scientist in the Land of Genomic Promise followed by Steven Chu on The Role of Genomics in Energy and the Environment. This followed panel discussion by imminent scientists. The entire conference and the content has been summarized below:

1. Eric Lander: How Biology Entered The Information Age

Eric Lander was one of the leaders of the effort to sequence the human genome, and has continued to work on various follow on projects through his involvement with the Broad Institute, a leading sequencing center. So, he makes an excellent choice to provide some perspective about how the growing availability of genomes has driven the biological sciences over the last decade.

“How do you ask how to read DNA?” Lander asked. “You ask the master—the cell. The cell is in the business of reading the information in DNA.” Molecular biology and biotechnology developed around the purification and use of the proteins used by the cells themselves to manipulate DNA.

Conceptually, Lander said, the key step was the development of a hierarchal map. Lay out genetic markers on a map, identify the DNA associated with those markers, and then dig down into the actual DNA sequences. The first human genetic map appeared in 1987, and that set the stage for the genome sequencing to kick off in earnest in the 1990s. The final draft was announced in 2003, on the 50th anniversary of the Watson and Crick paper.

More detail can be read at: http://www.nobelweekdialogue.org/science/eric-lander-how-biology-entered-the-information-age/

2. Nowotny-Horizon 1620 and beyond

Nowotny compared the new EU funding strategy, Horizon 2020, to what she called “Horizon 1620″. This was the year which Francis Bacon “sailed through the pillars on knowledge”. Bacon and others promised “the effecting of all things possible”. She cited an important part of this enlightenment era as the belief in progress.

Looking back at the industrial revolution, Nowotny said “it was only when [technology] came together with science that it became the driver that we see today”.

Towards the end of the talk, Nowotny spoke about ethics and promises. Politicians across the world should listen to this wise nugget: “Be careful with promises we make and not to betray them.”

3. Understanding gene environment interaction

In the panel discussions that took place after the main lectures were interesting and added more flavor to the debate.

he moderator, Göran Hansson, posed the question: How far are we from understanding these interactions?

Eric Lander raised a really interesting point that the general public perceive genetics as risk factors of disease. He disagreed with this impression saying “genetics is here to understand mechanism”. It seems that geneticists need to portray as Lander said that “genes and environment works inextricably together”.

Using lung cancer as an example, Lander said that we can understand the genes involved but we need to address the huge environmental factor: smoking. He added that we need to communicate science better to get people to stop smoking and understand this obvious environmental effect.

In some diseases, I thought it was brilliant that this panel of geneticists were willing to question the focus on genetic research. Joe Goldstein said “we have to deal with patients with diseases that have strong familial components”. He cited colon cancer as an example where a colonoscopy is much better than getting your genome sequenced.

If you look at cancers in a population, the hereditary impact varies between 3 and 10%. Using breast cancer as an example, Mary Claire King said that by working with families that are severely affected by the disease, they were able to isolate the genes involved: BRCA1 and the many others found since. She said Europe was better at testing for these mutations but the United States needed to improve. If these mutations are tested in women, these cancers can be prevented. I think this is true for many new technologies involving genetics – governments are slow to adopt them which to me seems short-sighted given the costs involved downstream for treatment.

This short-term focus was also raised by Bert Vogelstein who said that “we, as a society, are so focused on curing these advanced cancers that we don’t see other ways to tame the beast”.

This was such an fascinating discussion. Now that we know so much more about the genetic mechanisms, it seems that looking towards the impact of the environment is more possible. Göran Hansson  summed this up saying “we are probably in for a new era of diagnostics”.

4. Future of Human Biology

There was a strong focus on the continued need for fundamental science during this afternoon’s session, Human Biology: The Great Deal We Don’t Know and How to Discover It.

The worry about reduced funding for fundamental research was evident during each speakers input to the conversation on the future of research on human biology. Taking this a step further, Christiane Nüsslein-Volhard said that “we need to know more about general biology”.

The moderator, Bruce Alberts, said that much of the funding for biochemical research is by people who have had these diseases e.g. cancer survivors. This has an adverse impact according to the Editor-in-Chief of Science. He often hears people say: “Why should the public tax money pay for scientists satisfying their curiosity?”

Craig Mello added that those very naive curiosities often result in huge discoveries. He mentioned being in awe of the fact that the genetic code is similar across organisms and finding out that the insulin gene can be read by bacteria. I interviewed him earlier this week and he spoke about this: read here.

“Curiosity is a basic must for scientists” said Nüsslein-Volhard. She recommended that if you’re not curious, don’t do science. Here’s a great formula she gave for good research:

Curisosity + Good Problem + Bit of Smartness = Good Basis for Research

Mello said that the reduction can be blamed on the limited resources we now have. Given the choice between funding research that might get into clinics next year or a long-term project that could revolutionize medicine, review panels are choosing the applied clinic-focused research. He said that funding in the United States is flat despite the increased need to understand the new knowledge available. “This is really unacceptable and it really threatens our ability to do the basic science for the next 10 years”.

Asked how we can change this, Steven Chu said that leaders have to be convinced that you have to make investments into the future. This is happening in the United States according to Chu who used the saying “you don’t eat your seed corn”. Mello added that we need to do a better job at communicating with policy makers and scientists must keep track of the impact of their research.

This is yet another conference where this debate is a hot topic. Every Nobel Laureate and prominent scientist that I have heard speak about this thinks there is a problem with fundamental science funding. However, policy makers in many countries think we need more applied science. Perhaps this is a take home message for policy makers!

5. Genetics and Agriculture

The afternoon stream was a panel session moderated by Matt Ridley, with panellistsDominic BartonTorbjörn Fagerström, Louise FrescoChristiane Nüsslein-Volhard andTikki Pang (Pangestu).

We began with two audience polls, a show of hands proposed by Ridley: how many people are in favour of GM foods? An overall majority in favour. Louise Fresco suggested a poll on how many are optimistic we can feed the world in 2050, again a majority. These two questions highlight the main themes of the discussion, that of the base issue of GM acceptance, and the need for which GM will be required to feed a growing population.

Fresco opened by stating the GM debate by highlighting that most of the GM work has gone into herbicide resistance, which ironically has generated the most resistance in another area – society. In recent years Bacillus thuringiensis toxin (Bt) has had a positive effect on health and ebnvironment, it has allowed small farmers in India and China to reduce use of pesticides, with a positive effect on health and environment. Can we extend that same duel benefit to other crops?

However Fagerström raised the more fundamental issue, the question of why is there this resistance in society? Especially given the empirical support for GM not being a problem is very strong. How did we end up here? Nüsslein-Volhard believes the issue is rooted in a resistance against science, rather than GM itself. Why do people not trust scientists? Why are politicians inclined to embrace the more fluffy ‘green’ organisations rather than scientific manifestos? The problem is that there is deeply rooted mis-trust brought about by a lack of education. I could liken it to the issues raised by Helga Nowotny this morning on the fulfilment of promise – genomic technologies meeting a pre-genomic society. After all, we have the genomes for several crops now (e.g. rice) so we actually know what we are changing.

The other issue is that in modern, western farms, farmers are paid whether their crop fails or succeeds; they just don’t need to care about more efficient production. In fact, if they increase production – the surplus just floods (and destablises) the developing countries. However, local action on governments in countries where these technologies are being developed negatively effects the prospects for these products in these developing countries.

Fresco highlighted that in discussing GM people don’t go into the details; there is too much generalisation. Focus on specifics, like perhaps the potato. We’re not talking about wide-crosses here (i.e. jellyfish genes in vegetables), but in fact practise sys-genesis, the back crossing with ancestral Andean types of potato that are resistant to phytophthora blight. We should show that GM can be close to the original, rather than some mutant chimera. Torbjörn agrees, and suggests that GM should be judged crop by crop like anything else. It’s like saying you are against electricity, just because some electrical items can be bad!

Another problem is that societies that most object to GM do not readily feel the tangible benefits of GM. Is the a comparable objection to GM cotton that we wear, or the idea of fast growing GM trees, or transgenic mosquitoes that don’t vector diseases such as Dengue. When we feel the advantage, so our perceptions of ‘risk’ diminish?

All in all, it was a productive event and provided a balanced point of view from scientific perspective and generally too.

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Junk DNA theory debunked


ENCODE reports 80% DNA functional by Muhammad Adeel

It is an oft quoted phrase that more than 98 percent of the DNA is junk or non-coding. The Human Genome Project did give us the sequence of the genome, but there was little insight into how the “A,T,G,C”s interacted in the code. However, our ignorance in this matter has lessened with each passing day. An initiative was launched in this regard known as ENCODE. It was an international venture and the acronym spelled for “Encyclopedia of DNA Elements”. The intention was to find any nucleotide that had something to do with expression in the genome. The bottom line of the finding is quite clear in negating the “junk” DNA theory. It indicates that more than 1.5 percent of the DNA is coding and is involved in expression! The finding comes after a decade of hard work of as many as 442 scientists from across the globe. Another important finding is that even the non-coding genome has something to do with “functional elements”.

According to Ewan Birney, the Lead Analysis Coordinator, “It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.”

Important things that have come to light are:

  • Non coding regions have docking sites where proteins can bind and this ultimately affects the expression of genes in the vicinity.
  • Other non-coding regions are transcribed into RNA but not translated to protein. Still, they have an effect on how the DNA is folded and packaged.

So basically, this DNA is not junk and hence 80% of the genome has some function.

Previously we had known that only 1.5 percent of the DNA is functional. ENCODE has reported that another 8.5 percent has coding regions where the proteins can adhere to DNA. The rest of the functional elements in the ENCODE analysis cover other classes of sequence that were thought to be essentially functionless, including introns. “The idea that introns are definitely deadweight isn’t true,” said Birney. Even some repetitive sequences—small chunks of DNA that have the ability to copy themselves and are typically viewed as parasites—are likely to be functional, often containing sequences where proteins can bind to influence the activity of nearby genes. Perhaps their spread across the genome represents not the invasion of a parasite, but a way of spreading control. “These parasites can be subverted sometimes,” Birney said.

Another important finding through ENCODE has been in new disease leads. The ENCODE researchers also found new links between disease-associated SNPs and specific DNA elements. For example, they found five SNPs that increase the risk of Crohn’s disease, and that are recognized by a group of transcription factors called GATA2. “That wasn’t something that the Crohn’s disease biologists had on their radar,” Birney said. “Suddenly we’ve made an unbiased association between a disease and a piece of basic biology.”

For more detail, the publication of ENCODE in Nature can be downloaded by clicking on the link below:

http://www.nature.com/nature/journal/v489/n7414/full/nature11247.html

-Adeel

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One step closer to artifical life


Artificial Life Not Just A Myth Anymore by Fatima Ahmed

Artificial life (often abbreviated ALife or A-Life) is a field of study and an associated art form which examines systems related to life, its processes, and its evolution through simulations using computer models, robotics, and biochemistry. Scientists in different institutes have been working in this field trying to create a life form artificially. The advent of new technology has enabled them to use computers to design softwares that can actually encode a living organism and reproduce it imitating the traditional biology of life forms. Over the years attempts have been made to create genomes with softwares but what was lacking was the formation of a single cell that could survive on its own.

Artificial life was a myth in the past, which later became a dream, then a goal and now a reality, when 5 days ago, the scientists at Stanford University and the J. Craig Venter Institute finally succeeded in developing the first ever software-based stimulation of an entire organism, a parasitic bacterium called Mycoplasma genitalium, which lives in the genital and respiratory tracts of humans. Though the organism was only a single celled one, it has laid the foundation of evolution of modern science & technology. According to The New York Times, it took 128 computers to operate the stimulation in which the tiny bacterium’s entire lifespan is chronicled at the molecular level. The program was so complex that Markus W. Covert, an assistant professor of bioengineering at Stanford University, said, “running a stimulation for a single cell to divide only 1 time takes around 10 hours and generates half a gigabyte of data”.

The scientists and other experts said that the work was a giant step toward developing computerized laboratories that could carry out many thousands of experiments than it is possible now, helping scientists penetrate the mysteries of diseases like cancer and Alzheimer’s. For medical researchers and biochemists, stimulation software will vastly speed the early stages of screening for new compounds.. And for molecular biologists, models that are of sufficient accuracy will yield new understanding of basic cellular principles. Thus artificial life can now help us to yield better quality of natural life.

-Fatima

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Latest on Personalized Medicine


Personalized Medicine-A Perspective

With the advent of Human Genome Project, the domain of personalized medicine has developed. However an important thing to realize is that the human genome presents somewhat of a “moving target”. This means that we are still a long way from interpreting the individual genome accurately. The complete premise of personalized medicine borders on the fact that we are able to assess the personal genome of an individual accurately.

A very simple example of this mobility of the genome is represented by hair loss in men. This indicates that the genome structure is changing with age. This phenomenon is now being studied by Kiho Cho at the Shriners Hospitals for Children, Northern California. This concept of hair loss can be similarly applied to disease based phenotypes as well. Juvenile cancer cases are less than adult cancers.

Cho and his co-workers have reported their findings in Experimental and Molecular Pathology. The purpose of this study has been to study the genome changes as per the age. Transposon activity of retroelements has also been noted to provide a clearer picture. Cho found that in mice liver tissue, the size of the genome increased with age. Furthermore, he and his colleagues were also able to find that the copy number of retro elements (of sub families) had increased by two fold. Their findings are important in the sense that now we know that retro elements will play a better role in the understanding of personal genome.

“DNA is changing spatially and temporally, meaning that within one subject — in this case an inbred mouse — depending on the tissue type, the structure of DNA is different,” Cho says. “And also, depending on the age, within the same tissue type, the DNA structure is changing. It is likely that DNA structure is unique for the individual cell, although we don’t yet have as much data on that as we would like at this point.”

An important insight that can be derived from this study is that now personalized medicine faces a newer challenge before it can be made common. New research and revision of protocol is required for better interpretation of the structural transformations of any individual’s genome. The next thing that would be targeted is whether these changes are cell specific or not. This would be helpful for cancer related studies.

Cho is of the idea that if we are able to highlight the structural changes and their correlation with diseases process, we would be able to come up with better prognostic markers.

 

 

 

 

 

 

 

 

-Adeel

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Investing in Biotech


Economic Perspective and Investing in Biotechnology

InVitro Vogue is an integrated biotechnology company in Pakistan and abroad with a scope to harness the hidden revolution. This company targets various aspects and labels the gap between academic research and industry utilization as the major factor in an unstable economy. Present times have seen a global economic slump with even the emerging economies like Brazil and India slowing down. Europe has been slow to recover and America is still suffering from aftermaths of the fiscal meltdown.

For developed countries and even the developing ones, biotech is a bright economic perspective. Biotech shows remarkable cost effective in its products. For instance, genome sequencing cost has dropped down to a staggering $1000. (Check out this TEDx talk for more detail: http://www.youtube.com/watch?v=oj-Lr6jCuls) Now this technology has the potential to redefine the diagnostic parameters of the coming decade, and at a very low price. Countries that have invested in such science and technology are bound to be rewarded in the coming decade.

In order to prove this, we can take a look at the Human Genome Project. When it was launched, it took in a lot of money ($3.8 billion). However, the payback was overwhelming. The economic activity generated from this project is around $796 billion and the personal income figures are $244 billion. The number of jobs generated from this project was a staggering 310,000 in the year 2010 only. This project has advantages not only in health care but agriculture as well. Gene therapy has also benefitted from it. So, biotechnology always leads to an “integrated” economic benefit.

It’s a matter of simple arithmetic. The more the country invests in research and development, the more are the returns. America has been cutting its funds for the last few years, and hence its GDP has suffered. If one were to take a look at China, they have increased their funding by at least 10 percent each year.

Another important element is the kind of technology that is being invested in. Much has been talked about America’s ill investment in Solyndra (Solar energy) but one needs to see which the positive avenues are. Another related factor is the type of regulations that exist for launching biotechnology products. America has quite stringent policies and many biotech entrepreneurs are of the opinion that this has led to a decrease in the innovation in biotech related research. This is important when we are talking about drugs based innovation. An ironic quote that needs be mentioned here is from Kiran Mazumdar Shaw, founder of Biocon. She says, “It takes 12 years to get a drug from conception to market, while it took six years to get the Airbus A380 from the drawing board to flying in the skies.”

So, at a global level, the paradigm needs to shift for helping the economy. Do mail your comments at:

adeel@invitrovogue.com

The human microbiome


Human beings can be thought as an ecosystem walking on two legs, every human being is carrying microbes 10 times greater than the number of body cells and far greater than the number of human genes. Determining such a dizzying number of bacteria, which are inhabitants of human body, is just like that we are exploring a new planet. In addition to telescopes and charts which are necessary for identification and characterization of a new planet. We need much more to explore the territory of the microbes which reside our body known as “microbiomes”.  A microbiome is the entire aggregation of microbes their genome (genetic element) and environmental interaction in a specific environment.

A consortium of researchers designed Human Microbiome Project (HMP), for characterization and identification of healthy and diseased human microbial flora. The HMP is a five-year collaboration of sequencing centers, dozens of board institutions and multidisciplinary research institution of different countries. The basic purpose of the HMP was to establish a cornerstone for understanding the particular interaction of microbes that how they exist within their human host. To achieve this goal, the scientist at the board had played a leadership role in creating molecular tools and in optimization and application of standard protocols. In addition to this, they also work in generating enormous amount of data, in development of new and innovative analytical techniques for understanding the data and for distinguishing microbiome’s the unidentifiable organism for genome sequencing.

For the first time, this consortium of scientists is going to answer two important and basic questions about the microbiota of healthy human beings: who’s there and what is there role? The answers of both questions are in a series of 14 scientific publications from the consortium. Two of the publications will appear in Nature on the 14th of June and 12 will be in Public Library of Science journals. “As 10 years ago there was Human Genome Project, envisage of HMP is to provide baseline for further studies related to human disease and health. This is an immense resource, which is now available publically to the scientific community. This data resource will allow us to ask two basic questions that how why microbial community varies” said by Dirk Greves, a group leader at the Board of Genome Sequencing and Analysis Program, among the Co-first author of one Nature paper and co author of other publications.

For HMP, samples were taken from 18 different body sites which basically target five main body organs, airways, skin, oral cavity, digestive tract and vagina. Two forty two healthy people ranging from 18 to 40 years of age, living around Houston or St.Louis, donated their samples. Surprisingly diversified and exuberant microbiota (microbial communities) composition was obtained. Moreover, microbes can widely vary not only from site to site in single person, but also from individual to individual, in a sense that certain bodyparts are more predictable than others. A wide variety of bacteria populate human saliva of one person, but people living in one community have the same kind of bacteria in their saliva. However, the bacteria residing the skin vary greatly from a person to person, but a moderate variety of bacteria were present in an individual. In the snapshot of Western human microbiome, Ethnic and racial background provides a strong association for microbial diversity. Surprisingly, instead of all the differences in microbial population of same body site of different individuals, all collected microbes perform same metabolic task that is break down of energy resources.

Typically, scientists studied bacteria through culturing them in laboratory dishes that will miss less abundant and non-culture able bacteria. HMP scientists resolved this problem, as they isolated DNA of more than 5,000 samples collected from healthy individuals. First objective of the study was that what types of microbes are present and how many of them are there. This was achieved by 16S ribosomal RNA gene sequencing. This is a specific gene, which is shared by all bacteria, but is not the property of humans, provides a barcode which can be exploited to identify and count the number of bacteria present.

Once this cumbersome 16S ribosomal RNA sequencing challenge will accomplish, scientists will also the whole DNA of all bacteria in a given sample. Then, on the basis of the DNA sequence they will create metagenome sequence, by combining the data of millions of small sequences. The metabolic capabilities of microbes can be explained with by sequencing all the genes of a microbial community. Before, doing all this, collaborators need to design such protocol whose results are not centre specific and a wide variety of scientific community can also use it. Board scientists are also working with other centers to establish a protocol that will be used to sequence extremely small amounts of DNA. Once this aim is fulfilled, new analytical methods will be required to decode these larger data set. Scientists have designed a protocol for identification of sequence errors known as chimeras. It is thought that  microbial metagenome contain 8 million different protein coding genes, which are 360 times greater than that found in human genome. It is the need of hour to establish and design new protocols to assign identity and function to this metagenome data.

According to Dolye Ward, scientist of the Board institute and co-author of both Nature publications, big science is hard and Metagenomics science is also hard, so collectively Metagenomics big science is square of hard. Crutis Huttenhower has contribution in decoding complex metagenomes, relied upon information collected from reference genome of representative members of microbiome. But, metagenomic approaches illustrated that reference genome was incomplete. It also allowed scientists to figure out distinct microbes from already sequenced organisms that no one has either identified or characterized even their genetic relatives. Scientists have narrowed down their priority list to 119 microbes, to round out the picture of microbes linked to healthy human being. After setting the foundation, the exploration is accelerated.

A note worthy and interesting fact was that the human being, from which samples were collected, were healthy but, bacteria residing them can cause disease. For example, Staphylococcus aureus strain responsible for drug resistance MRSA was present in the noses of 30 percent people. Most of the time these pathogens peacefully co exist with human beings. Scientists are interesting to explore the factors which tip these pathogens, living peacefully in human being, toward disease. HMP has produced a catalog of micro-organisms who have co-evolved with humans. Next focus of scientists is to explore that how the microbiome affects inflammatory bowel disease and type 1 diabetes. They are also exploring options for early prediction and diagnosis of disease and even therapeutic manipulation of microbiota.

-Adeel