An interview with Tarjani Agrawal (NCBS) : eLIFE spotlight on early careers.


Tarjani Agrawal is currently completing her PhD in neurogenetics at the National Centre for Biological Sciences, India (NCBS). After her PhD, she would like to move abroad and continue working in research as a postdoctoral fellow. In her spare time, she enjoys swimming.

How do you describe your research to your friends and family?
Fruit flies are like tiny flying robots. They beat their wings one hundred times a second and can change direction in just a few milliseconds. However, we don’t know which neurons in the brain co-ordinate with the muscles used to fly. I try to explain flight as a well co-ordinated motor behaviour like walking, swimming and running. I am looking for the neural circuits that keep flies airborne.
What attracted you to studying neural circuits in fruit flies?
While flying, fruit flies rely on information from multiple senses, including smells and sights. To me, using genetics as a tool to find and study the neural circuitry for flight in fruit flies is like connecting the pieces of a puzzle. Every piece of information that we get gives us a hint about the next piece, which could be just one piece amongst thousands, but will have a unique structure and role. And the outcomes always make us more curious.
What was the main finding in your recent eLife paper?
Calcium ions are used to send signals in many biological processes, especially in neurons. It has been debated whether dFz2, which is a receptor protein present on the outer membrane of neurons, acts via calcium signalling. Our study shows that it does (Agrawal and Hasan, 2015). This signalling regulates flight by making an enzyme called tyrosine hydroxylase in dopaminergic neurons. Going a step further, we found that PAM dopaminergic neurons, which form a cluster of about 120 neurons towards the back of the brain, stimulate a brain region called the mushroom body. The activity of this circuitry is essential for the maintenance of flight.  
Why is this finding exciting?
The mushroom body has always been studied in the context of olfactory memory formation and reinforcement—the ability to remember and respond to odours. Our study shows that it is also involved in the regulation of a well co-ordinated motor behaviour: the flight of fruit flies. This changes the perception of the mushroom body in the field—now it can be thought of as a junction for various processes, including olfactory memory formation, visual learning and mating, as well as motor behaviour. 
What are you working on at the moment?
I previously found that a receptor protein called PdfR, which is a regulator of circadian rhythms in flies, also regulates flight (Agrawal et al., Plos Genetics 2013). Currently, I am investigating whether there are any common roles of PdfR in circadian rhythms and flight. I am using different light conditions to either disrupt or maintain circadian rhythms and then testing how this affects the ability of the flies to fly. 
What has been your best moment in the lab?
It would be that Sunday when I saw that an increased amount of tyrosine hydroxylase in the PAM neurons of dFz2 deficient flies is sufficient for flight. I got goosebumps seeing those flies flying for longer time periods. 
And the worst?
The worst day would be when I was trying to do multiple experiments in one day ranging from western blotting, flight assays, dissections and confocal imaging. By the end of the day none of these experiments had given any conclusive results. It was then that I decided that I would plan only one type of experiment for each day. 
Who has most influenced your career so far?
My PhD guide Gaiti Hasan has inspired me in multiple ways. Her thinking and ideas have influenced my scientific approach and made me the researcher that I am today. I have learnt a lot from her, especially how being proactive helps in doing good science. 
What single change would most improve the way that science is done today?
There is lot of competition in the field of science, which sometimes leads to criticism as well. What I think would really help is more constructive criticism. This can push someone to perform better.
What would most improve the professional lives of early career scientists?
The only advice I have is ‘Be positive and keep going’. This mantra has influenced my life tremendously and encourages me to do better at every step.
What advice would you give to someone who is considering a career in science?
If you are curious and love science then the sky is the limit. While performing experiments in the lab, you will have exciting moments as well as really dark times but the only thing that helps is being interested. So, do something that you would really like to do.  
What is India like for science?
I would say India is a great place to do basic learning, as technology is not used as much during early education, which leads to a lot of learning by trying new activities and practising them. However, for higher and more sophisticated scientific research demanding complicated tools and techniques, India is still developing facilities and building infrastructures that will make it a better place for science in future.  
Why would you like to go abroad for a postdoctoral position?
I feel that knowing and collaborating with different scientists all across the world is very beneficial. Doing my postdoctoral work abroad would give me a better opportunity to interact and discuss my work with many more scientists. It would also allow me to learn personally from the experts in the field and explore challenging and interesting problems.
What are your main interests outside science?
I try to engage myself in lots of activities outside the lab. Some of my favourites are travelling, playing board games like checkers and monopoly, and sports like badminton and squash. However, listening to music while swimming tops my list.
Do you find it difficult getting the work-life balance right?
Mostly not. I try to catch up with friends and family from time to time. I should mention that this is something that I have learnt from my PhD supervisor. 
Where would you like to be ten years from now?
I would like to be an independent scientist with a dedicated lab space studying how multiple behaviours are integrated and the influence one behaviour has over another. 
What would we be surprised to learn about you?
Social behaviour among fish has always amazed me. I wanted to explore size-based hierarchal organisation among clownfish. After joining NCBS, I learnt that studying fruit flies is much easier, thanks to all the genetics. However, I still maintain a bowl of two blackmoor goldfish and a few guppies in my house. 
Is your spouse/partner/significant other a scientist? 
While my eLife paper was in review, I was on leave to get married to a non-scientist. He is an engineer by education, and he always gives me a different perspective of my own work. 
What does he do? 
He is a financial analyst, working in New York for an investment bank. He deals with huge data sets analysis and advises me on how I can handle highly variable huge datasets.
If you could commission eLife to interview a scientist who you want other early career researchers to be inspired by, who would you nominate and why?
I would definitely nominate Prof. K. VijayRaghavan, Secretary of Department of Biotechnology, Govt of India and former director of National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore to be interviewed. He holds a lab at NCBS exploring the neural circuitry and developmental program for the walking behaviour of fruit flies. He is a wonderful scientist and has a dynamic personality. Every discussion with him—either scientific or non-scientific—leaves you with a wonderful feeling of positivity and hope. I still remember the discussions I had with him during initial years of my career and they are still inspiring. Despite being extremely occupied and busy in his schedule, he was always available for discussion and would later remember every detail about it. I am certain anyone who has met him or known him cannot be left uninspired by his achievements and personality.    
Tarjani Agrawal CV
2009-present: Integrated PhD in neurogenetics, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 
Summer Program during 2006-2009: Diploma in Biology, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore
2006-2009: BSc in Biochemistry, Sri Venkateshwara College, University of Delhi, New Delhi

Original Article :

Evolutionary Battle for Supremacy : Mystery of Sex Chromosomes


Image : Science Photo Library

          New DNA sequencing data reinforce the notion that the X and Y chromosomes, which determine biological sex in mammals, are locked in an evolutionary battle for supremacy.

David Page, a biologist who directs the Whitehead Institute in Cambridge, Massachusetts, and his colleagues explored the Y chromosomes carried by males of several species, mapping stretches of mysterious, repetitive DNA in unprecedented detail. These stretches may signal a longstanding clash of the chromosomes.

Page presented the results last week at a meeting of the Society for the Study of Reproduction in San Juan, Puerto Rico. His team’s subjects included humans and other primates, a standard laboratory mouse, and a bull named Domino.

“This idea of conflict between the chromosomes has been around for a while,” says Tony Gamble, an evolutionary biologist at the University of Minnesota in Minneapolis. But the sequencing data from the bull’s Y chromosome suggests that the phenomenon is more widespread than previously thought, he adds.

The mammalian Y chromosome has long been thought of as a sort of genomic wasteland, usually shrinking over the course of evolution and largely bereft of pertinent information. Page’s work has helped to change perceptions of the Y chromosome by revealing that it contains remarkable patterns of repeating sequences that appear dozens to hundreds of times 

But the structure of these sequences and precise measures of how often they repeat have been difficult to determine. Standard sequencing technologies often cannot distinguish between long stretches of genetic code that differ by a single DNA ‘letter’.

Letter by letter

Page and his collaborators avoided this problem by using what he calls ‘super-resolution’ sequencing (a technique better known as single-haplotype iterative mapping and sequencing, or SHIMS), which can detect such minute variation between lengthy segments of DNA.

The team sequenced many large, continuous stretches of the Y chromosome and carefully scrutinized the areas that looked as if they overlapped. They found that repeating structures make up about 24% of the accessible DNA in the human Y chromosome, and 44% of that of the bull.

And in the Y chromosome of the mouse, which is much larger than that of a human, repeating structures make up almost 90% of accessible DNA. The intricate patterns, which often contain palindromes — sequence that reads the same in forward and reverse order — carry three families of protein-coding genes. What the genes are doing — and how they got there — remains a mystery, however.

In mammals, the X and Y chromosomes emerged relatively recently from a regular pair of chromosomes before differentiating from one another. They share many of the structures that came from their ancestral source, but these repetitive regions seem to have come from somewhere else.

The repeated genes in the mouse Y chromosome do not resemble anything on the human Y chromosome, but they do have analogues on the mouse X chromosome. And in the mouse, human and bull, the repeated genes on Y and X are expressed in the male germ cells that eventually produce sperm.

A biological black box

Taken together, Page argues that this is evidence that the genes are involved in meiotic drive, a somewhat mysterious biological process that subverts the standard rules of heredity. In it, a particular version of a gene — or in this case, an entire chromosome — manages to increase the frequency by which it is transmitted to the next generation.

How that works is unclear. Sperm carry an X or a Y chromosome; genes expressed in the testes, where the cells are produced, may influence which sperm will be more likely to successfully fertilize an egg.

Previous studies lend credence to this idea. A team led by geneticist Paul Burgoyne and collaborators at the MRC National Institute of Medical Research in Mill Hill, UK, found that mice with a partial deletion of the Y chromosome produce offspring with a female-skewed ratio. The researchers subsequently shifted offspring sex ratios in both directions by tinkering with the expression of these multicopy genes.

Of course, mice — in nature and in the lab — usually maintain even sex ratios. Failing to do so could harm species survival. So as these Y-promoting genes made copies of themselves, subsequent mechanisms evolved to suppress their selfish urges. Page’s results provide a way to explore that evolutionary history; the data on the bull genome suggest that the mouse X and Y may not be exceptions.

With further high-resolution sequencing data, researchers may find more support for genomic battles of the sexes and possibly uncover other surprises. “There’s this rich tapestry of what sexual chromosomes are capable of,” says Gamble.

Original Article : A battle of the sexes is waged in the genes – Brendan Maher

Link :

Learning to Survive: Evolvability in Bacteria exposed to Fluctuating Environments

Reported by Shanti Kalipatnapu , Jun 25, 2015


           Bacteria are known to thrive in an incredibly wide variety of habitats and conditions ranging from the human gut to hot springs. Scientists are trying to understand how bacteria manage to learn to survive in various conditions and thus to learn about the process of evolution itself. For this, researchers often perturb environmental variables such as temperature or pH, usually one at a time, even though in nature such variables typically act together. In an effort to study what is likely the situation in nature, the research group of Dr. Sutirth Dey at IISER Pune has chosen to expose bacteria to unpredictable fluctuations in multiple environmental parameters.

The group exposed bacteria to different combinations of conditions (pH, salt, hydrogen peroxide), where the successive environments were picked randomly. After 30 days the group monitored the growth rate of the bacteria.

Describing their observations, Dey said, “We had expected that the bacteria would do better in the environment in which they have been selected. This did not happen. Instead, we found that the growth rate of the bacteria was higher under conditions like antibiotics and heavy metals, environments that they had never experienced before”
On further investigation, the group found that this ability to withstand new environments/stresses is not related to an increased mutation rate and could instead be related to their increased ability to throw out toxins from the cell (efflux activity).
“We found that exposure to unpredictable fluctuations in the environment could itself help bacteria evolve an increased ability to throw out toxins, including antibiotics, from the cell at a faster rate. This surprising observation gives us new clues to understanding evolvability in bacteria”, said Dey summarizing their findings.
      It is commonly thought that injudicious use of antibiotics cause antibiotic-resistance in bacteria. This study opens the possibility that environmental variability can potentially lead to similar outcomes. Given that the climatic variability has increased greatly over the last few years, it is likely that bacteria could display resistance against drugs they haven’t been exposed to before. This could potentially have serious public health consequences.
This work has recently been published in the Journal of Evolutionary Biology (28:1131-1143) and was authored by Shraddha Karve, Sachit Daniel, Yashraj Chavhan, Abhishek Anand, Somendra Singh Kharola and Sutirth Dey.
This research received financial support from the Department of Biotechnology, Government of India and internal funding from Indian Institute of Science Education and Research, Pune.


Original News :