Cori Bargmann Puts Her Mind to How the Brain Works

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– In conversation with Claudia Dreifus, NYTimes

Cornelia Bargmann, a neurobiologist at Rockefeller University in New York, studies how genes interact with neurons to create behavior. Two years ago, President Obama named Dr. Bargmann, who is known as Cori, a co-chairwoman of the advisory commission for the Brain Initiative, which he has described as “giving scientists the tools they need to get a dynamic picture of the brain in action.”

I spoke with Dr. Bargmann, 53, for two hours at the Manhattan apartment she shares with her husband, Dr. Richard Axel, a neuroscientist at Columbia University. Our interview has been edited and condensed.

Q. As an M.I.T. graduate student, you made a discovery that ultimately led to the breast cancer drug Herceptin. How did it happen?

A. What I did was discover a mutated gene that triggered an obscure cancer in rats. Afterwards, it was discovered — by others — that this same gene is also altered in human breast cancers.

Since our work in the rat cancer showed that the immune system could attack the product of this gene, Genentech developed a way to deploy the immune system. That’s Herceptin. It is an antibody against the gene that sits on the surface of a cancer cell. It can attack the cancer cell growing because of that gene.

Q. Currently, you spend your time trying to understand the nervous system of a tiny worm, C. elegans. Why do you study this worm?

A . Well, the reason is this: Understanding the human brain is a great and complex problem. To solve the brain’s mysteries, you often have to break a problem down to a simpler form.

Your brain has 86 billion nerve cells, and in any mental process, millions of them are engaged. Information is sweeping across these millions of neurons. With present technology, it’s impossible to study that process at the level of detail and speed you would want.

Now, about 25 years ago when I was transitioning from cancer biology to neuroscience, this little worm’s brain had just been mapped — every connection between every nerve cell and the brain. That’s roughly 7,000 connections and 300 neurons. You could look at a brain cell — which you could see because the creature is transparent — and say, “I know what that cell does. I know what it’s connected to. I know what genes it expresses.” For a researcher, that’s a lot.

Q. But is a simple worm really an appropriate model for studying the human brain?

A. Most of what we know about the human nervous system, we have learned from simpler animals. The most famous animal in neuroscience is the squid because it has these huge nerves that enabled people to understand the basis of the electrical transmission of information.

In fact, one of the biggest surprises in modern biology is that the genes are not that different between the different animals. Almost every gene we are interested in with humans is recognizable in a mouse. Most are recognizable in a worm or in a fly.

Q. So what have you learned from your worm?

A. In 1993, we did an experiment showing that worms could smell. This wasn’t known before. Our next experiment, I think the most important my lab did, is that we made a worm neuron smell an odor it had never smelled before, and we made the animal completely change its opinion of that odor by doing that.

We had an animal that loves an odor that smells like a certain food it likes. Usually, the worm runs right toward the odor. We took the gene that is a sensor for the food from where it was normally supposed to be. We put it into a different neuron that senses things the worm finds dangerous.

Then, we “asked” the worm what it thought of this smell it usually loves. It ran away from the smell, as if it were dangerous.

This said that the odor-sensing nerve cells form an innate map where each one knows whether something is good or bad about the environment. There’s a completely unlearned internal set of preferences, a set of instincts about what’s good and bad.

Q. For the past two years, you’ve headed the advisory committee to the Brain Initiative. On the phone, you told me that the experience made you into a better scientist.

A. In the lab, you have to make choices about what you think is important. On this commission, we had to do something similar.

Our problem was this: There was an appropriation of $100 million for the first year. That’s a limited amount of money. We didn’t want to be in a situation where you’re giving $14.99 to every neuroscientist and calling that a Brain Initiative.

So then, what to invest in that will move the science forward? What parts of the field are coming along? What is science fiction? Eventually, we came to an agreement on a basic outline: Use the money for mapping brain activity in circuits and networks.

The first step is to create new and improved technologies to study the brain. With better tools, all of neuroscience will move forward.

The second step is to apply those technologies to make discoveries about how the brain functions. The theme is understanding brain activity, the flow of information through millions of interconnected nerve cells. The long-term goal is to use that knowledge to help prevent and treat brain disorders. That may be decades or more away.

Q. Some of your critics have complained that you don’t have enough funds to tackle such a huge question.

A. I do not think that the goal of the initiative is to map every connection or detect every neuron firing anywhere in the brain. The goal is to develop and apply new ways of studying networks of neurons involved in thought, emotion, perception and action.

Q. In recent weeks, there’s been a lot of renewed discussion of the role of women in science. Have you encountered much gender bias?

A.  On the whole, no, though on my graduate school interviews, I do remember someone asking why I should take a slot in graduate school when I was probably going to get married and have children. I thought, “You dinosaur!”

I didn’t get that message every day. I actually got a lot of encouragement. At M.I.T., I had a wonderful Ph.D. adviser, Robert A. Weinberg. In his lab, there was a postdoc from Europe who used to call the women “the bossy ladies.” One day, Weinberg heard this, and he took the postdoc into his office.

When the postdoc came out, he was pale. We never heard anything about that again. Weinberg is really a mensch.

Q. What were you like growing up?

A. I read indiscriminately. I enjoyed mystery stories. When I read “Microbe Hunters,” it seemed scientists were like detectives following a set of clues. Some clues were red herrings. Discarding them was an important step to getting to the right idea.

Original Source : The New York Times.


Shodhganga: A Reservoir of Indian Theses


        Theses and dissertations are known to be the rich and unique source of information, often the only source of research work that does not find its way into various publication channels. Theses and dissertations remain an un-tapped and under-utilized asset, leading to unnecessary duplication and repetition that, in effect, is the anti-theses of research and wastage of huge resources, both human and financial.

    The UGC Notification (Minimum Standards & Procedure for Award of M.Phil. / Ph.D Degree, Regulation, 2009) dated 1st June 2009 mandates submission of electronic version of theses and dissertations by the researchers in universities with an aim to facilitate open access to Indian theses and dissertations to the academic community world-wide. Online availability of electronic theses through centrally-maintained digital repositories, not only ensure easy access and archiving of Indian doctoral theses but will also help in raising the standard and quality of research. This would overcome serious problem of duplication of research and poor quality resulting from the “poor visibility” and the “unseen” factor in research output. As per the Regulation, the responsibility of hosting, maintaining and making the digital repository of Indian Electronic Theses and Dissertation (called “Shodhganga“), accessible to all institutions and universities, is assigned to the INFLIBNET Centre.

    Shodhganga” is the name coined to denote digital repository of Indian Electronic Theses and Dissertations set-up by the INFLIBNET Centre. The word “Shodh” originates from Sanskrit and stands for research and discovery. The “Ganga” is the holiest, largest and longest of all rivers in Indian subcontinent. The Ganga is the symbol of India’s age-long culture and civilisation, everchanging, ever-flowing, ever-loved and revered by its people, and has held India’s heart captive and drawn uncounted millions to her banks since the dawn of history. Shodhganga stands for the reservoir of Indian intellectual output stored in a repository hosted and maintained by the INFLIBNET Centre.

  The Shodhganga@INFLIBNET is set-up using an open source digital repository software called DSpace developed by MIT (Massachusetts Institute of Technology) in partnership between Hewlett- Packard (HP). The DSpace uses internationally recognized protocols and interoperability standards. Shodhganga provides a platform for research scholars to deposit their Ph.D. theses and make it available to the entire scholarly community in open access. The repository has the ability to capture, index, store, disseminate and preserve ETDs (Electronic Theses and Dissertations) submitted by the researchers.

   DSpace supports “Open Archives Initiative’s Protocol for Metadata Harvesting” (OAI-PMH) and uses a qualified version of the Dublin Core schema for its metadata. The INFLIBNET Centre, promotes setting-up of institutional and ETD repositories in member universities using OAI-PMH complaint software. A number of member universities have already set-up their institutional and ETD repositories using either DSpace or other OAI-PMH compliant Institutional Repository software. It would be possible for universities having sufficient network and computing infrastructure to maintain their own ETD repositories wherein their research scholars could deposit e-versions of their theses and dissertations. Moreover, they can use Shodhganga to host their theses as backup archives. INFLIBNET Centre, besides maintaining the Central ETD Repository (Shodhganga) would also deploy a central server to harvest the metadata from all such ETD repositories distributed in universities with an aim to provided unified access to theses and dissertations through its harvesting server.

   Shodhganga replicates academic structure of each University in terms of Departments/ Centres/ Colleges each University has to facilitate ease of navigation. This structure facilitates research scholars from universities to deposit their theses in the respective Department / Centre / College. As shown in the Fig 1, option for simple search and advance search are available on the home page along with browsing facility through universities and departments. The Centre is also developing a semantic web-based interface to facilitate subject-based browsing, navigation, search and retrieval of content available in the repository.

Source & Original Link : Shodhganga


A potential micro-RNA biomarker identified for diabetes in the Indian population

In search of a micro (RNA) solution to a macro disease (diabetes) (Photo: Muthuswamy Balasubramanyam)

          A recent study has identified microRNAs that are potential biomarkers for diabetes. At least one of them is specific to the Indian population.

          Diabetes, a disease involving impaired glucose metabolism, has assumed epidemic proportions due to its high prevalence worldwide. India is estimated to have more than sixty-two million diabetic patients, making it one of the epicentres of the global epidemic. The numbers are predicted to increase exponentially in the coming decades. Worryingly, the age of onset of diabetes in Indians is decreasing, indicating that in the coming years, a substantial section of India’s youth will be suffering from the disease. However, research on diabetes in India has been insufficient, making it difficult to formulate an adequate national response.

       Scientific efforts worldwide have focused on finding biomarkers that can aid screening and early detection of diabetes. Indians comprise the ‘Asian Indian Phenotype’, which refers to a gamut of biochemical and clinical peculiarities in the South Asian population that predisposes it to the disease. This makes direct extrapolation of data obtained from western populations to Indians difficult. This motivated a research group from Madras Diabetes Research Foundation (MDRF) to conduct a recent study focussed on finding a biomarker for diabetes specifically tailored for the Indian population.

“The most promising biomarkers should be robust and clinically translatable”, explained Muthuswamy Balasubramanyam, a senior scientist at the foundation and one of the principal investigators of the study. Circulatory microRNAs, small pieces of non-coding RNAs floating in the bloodstream, satisfy both these conditions—they are remarkably stable and require only a blood sample for testing—thus being ideal for large-scale clinical use. MicroRNAs are also known to be master regulators of gene function, affecting a variety of physiological processes. Research has shown that the level of circulating microRNAs changes consistently in various pathophysiologies like cancer and cardiovascular diseases, but little is known about its role in diabetes, especially in the Indian context.

Aiming to identify circulating microRNAs that could serve as biomarkers for diabetes, the investigators recruited three groups of subjects for the study: diagnosed Type 2 Diabetes Mellitus (T2DM) patients, subjects with normal glucose metabolism (NGT: Normal Glucose Tolerance) and those with pre-diabetic state of Impaired Glucose Tolerance (IGT). Blood glucose level was measured in all the participants to confirm the grouping. Candidate microRNAs were searched after characterizing the microRNA profile for each participant. “We found that four microRNAs had different serum levels in IGT and T2DM patients compared to control NGT subjects”, said Balasubramanyam. Levels of two of these microRNAs were also similarly altered in diet-induced diabetic mice, providing further support towards their potential usability as a diabetes biomarker. 

“Interestingly, among the altered microRNAs , miR-128 has never been described in previous diabetes studies and appears to be specific for the Indian population”, said Balasubramanyam. Considering that miR-128 has been earlier reported as a biomarker of cognitive impairment and that there exists a neurological component in the etiology of type 2 diabetes, Balasubramanyam speculated that miR-128 could be the connecting link for the cognitive dysfunction and/or depression associated with metabolic diseases like diabetes. miR-128 was further positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of altered lipid level associated with T2DM.

The results, though preliminary, are exciting because miRNAs are considered to have tremendous potential as non-invasive biomarkers for the screening, monitoring and diagnosis of a disease. The group plans to conduct long-term studies to elucidate the connection of these microRNAs with diabetes to facilitate their use as biomarkers in future. The day might come when a simple blood test would reveal the microRNA profile, facilitating pre-emptive screening of at-risk people. Effective prevention and management can then start right away, before the onset of the disease, which in turn, would lead to a reduction of the burden diabetes imposes on the in Indian nation and society at large.

Original News : IndiaBioscience