Influential Interview with Amitabh Joshi : On evolutionary biology, and a passion for science

Amitabh Joshi
Amitabh Joshi (Photo: Amitabh Joshi)

Thoughts on experimental evolution, problem-solving and how to pursue science with passion.

By – Anjali Vaidya,IndiaBioscience


How did you become interested in evolutionary biology?

While I was doing my BSc Honours in Botany at Delhi University, I found genetics very interesting, because it brought back many of the things that I had liked about math and physics. There was a lot to understand, rather than just a lot to memorize. I remember being particularly impressed with how Jacob and Monod worked out the operon. I still think that’s one of the most beautiful things in genetics.

So after my BSc I applied for admission to MSc genetics at Delhi University. We had a course in population genetics the first year, taught by Professor C R Babu. He was quite simply the most amazing teacher I’ve ever had in my life. Many of the things he said in class I can still remember after almost thirty years.

Population genetics was just beautiful—it was cute, it was lovely. I really liked it. And so I decided to go for a PhD in evolution, and ended up working with Larry Mueller at Washington State University.

There was a certain amount of contingency in the choice of subject. I could as well have ended up a professor of Urdu literature or philosophy. I was reasonably clear that I wanted to be in academics. I couldn’t then and I can’t now imagine being in any other profession.

Can you describe some highlights of your current research?

The approach that we take in our lab is called experimental evolution. Instead of using an existing species to infer what might have happened in the past, you work with an organism that allows you to observe several hundred generations within a few years.

What we do is set up evolutionary problems for populations of fruit flies to surmount. For example, we took one set of populations and said that only those individuals that become adults at the fastest speed are allowed to breed for the next generation. After seventeen years and 600 generations, these populations are the fastest developing line of Drosophila melanogaster that anybody has ever seen.

When we asked what traits were sacrificed for the sake of developing fast, we found that these flies areworse than their ancestors at surviving to adulthood. We also found that faster developing flies preferentially burn lipids over carbohydrates as pupae. This gives them more energy per microgram, but it depletes their lipid reserves, which reduces fertility. In these populations you have to first be among the fastest 20% to emerge, and if you burn up your fat reserves and lower your chance of survival to develop quickly, you will probably still have higher fitness.

Our recent work follows up on our observations that different competitive strategies can evolve under conditions of high larval density. Our evidence suggests that when a culture vial’s food column is very short, the build up of waste means that even though food is scarce, feeding faster will not help larvae survive. We are developing our results into a broader view of competitive ability that emphasizes the interaction between environmental context and larval density in the determination of density-dependent fitness.

We have also shown that density-dependent selection can lead to the evolution of more stable population dynamics. In collaboration with Dr. Sutirth Dey (IISER Pune) we are trying to develop integrated models of the evolution of both density-dependent fitness and population dynamics. These results represent the first major conceptual advances in density-dependent evolution and population dynamics since Larry Mueller’s seminal work in this field in the 1980s and 1990s.

What is the most satisfying research problem you’ve worked on?

When I was a grad student, I became interested in the so-called cost of sex problem in evolution. I found that there was a huge debate that had been going on for twenty years in the literature about what the cost of sexual reproduction really was. John Maynard Smith argued that it was the cost of producing males, while G C Williams argued that it was the cost of genome dilution.

I remembered from my BSc that dandelions and other asexual plants produce partially sterile pollen. But in all the models of the cost of sex, people assumed that plants that produce asexual eggs either do not produce pollen, or they produce pollen in equal amounts and with equal fertility as sexual individuals. So I built a model, which would look between these two extremes, treating the output and fertility of male gametes as separate variables. It very quickly turned out that the cost of sex has both components—cost of male function and the cost of genome dilution. If you model only these two extreme cases, you will either find that the cost of sex is due to the cost of male function or that it is due to the cost of genome dilution. Between extremes, there are both components to the cost of sex.

This work eventually grew into several papers with Professor Mike Moody in the Journal of Theoretical Biology. In terms of satisfaction, this is one of the most satisfying pieces of work that I have done. It solved an old problem in a very clean way, by showing that what you are seeing as a problem is the fact that you’re not looking at the whole picture—you are just looking at two extremes of the spectrum.

In some sense the work was all the more rewarding because there was no need for me to do it. It wasn’t part of my thesis work, or work that somebody had told me to do. It just grew organically out of something interesting that I studied in a course, and then led to eventually something very nice.

What advice would you give to people starting out in science?

If you do your work with a certain passion, your career will take care of itself, and you will enjoy yourself. When you work, the rest of the world should stop. And I don’t mean that you should work 365 days a year. You cannot plan that “Tomorrow morning from 9:30 to 10:30 am I will think of a novel hypothesis.” All my life, I have never been an organized, steady worker, but when I work, at that time I’m completely focused on what I’m doing—whether it’s writing a manuscript or analysing a particularly recalcitrant data set. At that point in some sense the rest of the world ceases to exist.

Nowadays, people view science too much as a career. I wish people would view science the way a classical musician views music. Of course singers earn money by singing, but they don’t think of it as a profession the way working in a bank is a profession. If your only aim is to publish in high impact journals, that can give you some measure of success within the parameters of the system. But I feel there are much more interesting ways of getting one’s kicks in science.

What are the most frequent misconceptions that you encounter regarding your work? Which questions do you dread?

The question I don’t like, but get quite often, is how is your work important to the upliftment of human society. Science is seen too much through utilitarian lenses. The purpose of science is to understand. Harnessing that understanding to practical use requires a very different mind- and skill-set.

The most frequent misconception nowadays is that every causal explanation in biology must coalesce to one or a few genes. This position is brainwashed into students by the time they come to grad school and does a great disservice to biology.

Can you talk a little about your own approach to mentoring?

Mentoring, to me, is the most important thing any of us ever do as academicians. Mentoring is the essence of our existence as a link in the continuing chain of human knowledge. It is not about giving a grad student a good problem to work on: it is about helping the student discover his or her own good problem. As Khalil Gibran said so beautifully:If he (i.e. a teacher) is indeed wise he does not bid you enter the house of wisdom, but rather leads you to the threshold of your own mind.

Ultimately, mentoring is about sharing. You share the logic of how you approach a problem, probing for the right fault line at which to attack. Too often, research supervisors just tell students what to do without really explaining why, and if the student asks why, it becomes an ego problem for the supervisor because it is interpreted as having their judgment questioned. People need to be encouraged to discover their own style of doing science. It is important to transmit to the mentee a whole world view, rather than just a set of scientific techniques.

Alongside evolutionary biology, you have found time to write Urdu poetry and study Indian history. How do your other pursuits feed into your research? How do you balance time?

I don’t think poetry feeds directly into science, or vice versa. Perhaps, at a more transcendent level, the spirit of poetry informs the spirit in which I do science. Science has its own beauty—there are models and formalisms that are astonishingly beautiful, as well as experiments that are beautiful in a way that makes you go vaah as if you had just read or heard a superb couplet.

I don’t balance time well. I cannot do things like say I will work on a manuscript before lunch and write a poem or read philosophy after lunch. I work episodically on all things, whether science or other interests. When I am in the frame of mind for something I become immersed in it, to the exclusion of other things.

What are your most and least favourite parts of your job?

Most favourite: teaching. Least favourite: listening in meetings to self-important people pontificate about what ails Indian science.

What is the best advice you have ever gotten?

From my mother: Jo kaam karo, theek se karo, ya phir mat karo. If you do something, do it well. Otherwise don’t do it at all.

Original Interview : IndiaBioscience



DBT partners Prakash Lab to spread microscope access


Rapid Fire

  • PrakashLab partner with DBT and its Star College programme.
  • Students in identified colleges starting with those under ‘Star College’ scheme will receive the Foldscope.
  • Students will join in Foldscope’s user-camps

Undergraduate students in all parts of the country will soon be able to take a peek at the world of microscopic organisms with a microscopethat they can take anywhere, following an initiative by the Department of Biotechnology to reach a PrakashLab’s low cost paper folding-microscope, the Foldscope (url) to them.

The ‘Foldscope’ has been developed by Dr Manu Prakash, an Indian-origin Assistant Professor at Stanford University. (URL)

The letter of intent exchanged between the Department of Biotechnology (DBT) and the PrakashLab in the presence of Prime Minister Shri Narendra Modi to distribute Foldscope through DBT’s star college and other programmes was a unique demonstration of how the government is was using the social media in novel ways to stimulate citizen science.

It all started with a tweet from Secretary, Department of Biotechnology Professor K VijayRaghavan to Dr Prakash on August 12 this year.

‘Hi, can we discuss using Foldscope widely in India? I am at the Dept of Biotech, Govt of India’.

Dr Prakash responded immediately welcoming it. A skype call followed subsequently. Prime Minister’s office also responded enthusiastically to the call requesting for his support.

Rapid communication through the social media played a crucial role quickly paving the pathway for the letter of intent to spread the low technology widely through DBT’s network.

Dr Prakash is excited about engaging through DBT to extend further the Foldscope’s reach to all parts of India. He said, “Our vision is to bring a microscope into the hands of every single kid in the world”.

It is a wonderful example of how small moves to connect with the world can translate already generated knowledge to our people.

“Partnering with PrakashLab’s Foldscope is an exciting new adventure for the Department of Biotechnology. It is Citizen Science at its best. The Foldscope is torchlight in the hands of human curiosity that allows each and every one of us to explore our planet at the microscopic level, just as the telescope allows us to explore the stars. The beauty we see and the science underneath it will create a new generation of young scientists in India. We look forward to taking this wonderful partnership ahead” said Professor VijayRaghavan.

PrakashLab, a research group at Stanford University working in the field of engineering and physical biology, will source Foldscope to DBT and its constituents.

The DBT will ensure that the Foldscope is provided to students of the Star College scheme in each identified college. This will be done progressively and staged based on the availability of Foldscope.

Foldscope will be used as an educational and training tool to understand physics, chemistry, biology and instrumentation.

Foldscope is provided as a kit where the student starts by first building the actual unit from the kit; and explores curiosity driven questions surrounding the microscopic world in physics, chemistry and biology. The users build an online community and share insights, projects, questions and scientific discoveries with the community at Foldscope online platform (URL).

Workshops and training programmes will be run by PrakashLab in collaboration with Indian institutions. The nascent Local Foldscope community based in India will also be involved in training.

After this initial pilot program, the collaboration with PrakashLab will be expanded to setting up of joint research for explorations of other low cost instrumentation in colleges as deemed mutually appropriate.

This was a case of matching of views that focused to create a spark. The Prime Minister has been stressing on using Indian experts abroad to bring benefits to India. PrakashLab with its vision of democratizing science develops low cost scientific tools that can scale up to match problems in global health and science education. Further connecting PrakashLabs to India can create magic through science driven by the young.

Source : DBT, India.

Serendipity in the Age of Search Engines:Biology in 3D

By Milka Kostic

  Milka is the Senior Editor of Chemistry & Biology and Structure.

I’ve always loved reading—one of the biggest punishments I ever got from my mother was for going to the library without permission.

My mom was at work, my dad on a business trip, and my younger sister at day care. I knew that my aunt was picking my sister up and bringing her home, and that she might arrive any minute, but I just couldn’t wait. The problem was that my aunt did not have the key to our apartment, and if I left, there wouldn’t be anyone to let her in. As this was all happening before mobile phones and text messages, I did the only thing I could: I left my aunt a hand-written note that the I’d gone out and that the key was under the door mat, and attached the note to the door.

I was so eager to get a new batch of books that it never crossed my mind that it might not be the best idea to leave a note that the key to our apartment was under a door mat and attach it to the very door! In the end nothing happened—I got my books, my aunt and my sister got into the apartment just fine, and we were not robbed. But I was still severely punished, as my mom did not appreciate this amount of independence in an eight year old. My aunt continued to joke about this and for decades would say “The key is under the door mat” to many of my brilliant ideas.

This and a few other misadventures along the way could not change who I am—an avid reader. The only thing that changed over the years is what I read. The largest shift happened when I entered college and decided to focus on science. At that point, large volumes of fiction and poetry were replaced by scientific literature, and although over the years fiction, and to a lesser extent poetry, came back into my sphere of reading interest, scientific literature still occupies most of my attention.

In my previous post I talked about how the way I read scientific papers changed as I transitioned from being an active scientist to a scientific editor. One thing that did not change, however, is the way I like to read when I have the luxury of a few moments of spare time. What I enjoy the most when it comes to reading is casting a wide net—going from a single sentence, or that one reference that captures my imagination, and following the trail of ideas and insights to wherever they lead. My starting point is often something that I know a lot about, but I also love starting from a chance glimpse that sparks my curiosity, and digging in.

You hear a lot about serendipity in science, and how unexpected discoveries go on to revolutionize entire fields. As with everything, a bit of it is part of the scientific lore, but anyone who ever did scientific research will tell you that this is actually true—the unexpected happens every day in little ways and does push forward science and our understanding of the world around us. You may also have heard laments of scientists of a certain age who remember going to the library, browsing journals just for browsing’s sake, getting immersed in an article just because, and walking away with a new idea that changed the direction of their research. In their view, serendipitous reading was made obsolete by search engines, online publishing, and keywords.

I am not convinced that the circumstances are as dire as that. A decade and a half ago you could still see me in the library, holding a pile of print issues of different journals in my hand, browsing, reading, re-reading, and flipping around. And sure, that did often lead to something interesting and unanticipated. But today is no different, except that the cozy chairs in the library have been replaced by a standing work station, and the source of initial inspiration comes from more places than a library shelf. These days more often than not my curiosity is nudged by something I see on social media. A simple tweet can snowball into an hour of intense reading and researching through scientific literature now at my fingertips. For me this no different from the good old library days, and the ideas or shift in perception that results from this process is no less valid or powerful than before.

The main enemy of serendipity is not search engines or keywords or social media—it’s the lack of time. So perhaps when people complain about not being able to freely browse and let their explorations of scientific literature go where they may, it’s really nothing to do with digitization of the content, or the fact that we might be too narrowly focused because all we do is use keyword searches. It’s all about the time pressure that we all feel and the need to get to our answers instantaneously.

At the end, you get what you pay for—and paying for a bit of serendipity with an hour of time is worth it to me. Sure, the work does not get done, or the house does not get clean, but in my world serendipity in literature discovery is still alive and here to stay. And I bet there are many of you out there feeling the same way! The main reason I say this so emphatically is that I believe we all, given an option and a blank sheet of mental paper, enjoy letting our minds go wherever they like, allowing ideas and thoughts to float and bounce. This seemingly aimless journey docks us at cognitive islands where treasures are buried, ready to be dug up. This thrills us to bits—and  that’s what serendipity is all about.

Taken From :         CrossTalkHeader

Contact, connect and fuse: An ultra-structural view of the muscle formation process


-By Anusha Krishnan,NCBS

For an avid exerciser, a muscle pull or tear is a painful and fairly common occurrence. A sudden turn or an unusually vigorous bout of aerobics can leave one with a muscle tear that will effectively confine a person to bed for a few weeks. However, muscles do heal – a set of quiescent cells called myosatellite cells in muscles are activated by injury to divide and form myoblasts, which in turn fuse with muscle cells to repair damaged muscles. The mechanistic basis of myoblast fusion with muscle fibers is now clearer thanks to recent work from Vijayraghavan’s group at the National Centre for Biological Sciences (NCBS).

Nagaraju Dhanyasi from Vijayraghavan’s group, has collaborated with Prof. Ben-Zion Shilo and Dr. Eyal Schejter at the Weizmann Institute of Science, Israel, who are also investigating the processes governing myoblast fusion in flies and mice. To study the process at a high resolution, it was necessary to generate electron microscope (EM) images. This allowed researchers to reconstruct the steps in the dynamic process of myoblast fusion, where the structure of the fusing membranes was closely examined. The work involved molecular biology and state-of-the-art electron microscopic techniques, which were carried out in collaboration with the EM facility of the Weizmann Institute. The team’s investigations have resulted in a description of the events during the merging of individual myoblast cells with muscle cells, and was published in the October issue of the Journal of Cell Biology.

Most of our knowledge about the fusion of myoblasts to form multinucleate muscle fibers has been gleaned from studies on the development of tubular muscles of Drosophila larvae. However, the mechanisms governing myogenesis (formation of muscle fibres) in striated muscles of the skeletal musculature in vertebrates is not very clear. This study focuses on the events occurring in myoblast fusion in Drosophila during the formation of flight muscles. These muscles serve as a particularly attractive model, since their developmental program, and their muscle fibre organisation resemble key aspects of vertebrate skeletal myogenesis.

“This work is actually a continuation of studies carried out by Vijay’s earlier students – Priyankana Mukherkjee and Rajesh Gunage”, says Nagaraju Dhanyasi, the first author of the paper. “Priyankana began this work by investigating the role of various fusion proteins using confocal microscopy in the myogenesis of flight muscles of Drosophila. This work was also a collaboration with Drs. Shilo and Schejter. Rajesh established the presence of stem cells in Drosophila muscles similar to the satellite cells in vertebrate muscles. This set the stage for addressing questions on vertebrate muscle regeneration in a Drosophila model system.” The advantages of using Drosophila as a model are many – the tiny fly is easily grown and is amenable to a huge array of genetic manipulations. In spite of this, the study of myogenic processes in flight muscles has lagged behind, primarily because tools for the genetic manipulation of later developmental phases were lacking. “With the advent of RNAi technology, this problem was solved, and we were able to study the myoblast fusion process in great detail”, says Dhanyasi.

The study shows that the fusion of myoblasts to existing muscle fibres, called myotubes, follows a set of distinct stages that requires communication between transmembrane elements and the actin cytoskeleton. An elegant series of experiments allowed the researchers to delineate the ultra-structural details of a series of discrete steps in this event. The process begins with myoblasts binding to the surface of an existing myotube with the help of a host of cell adhesion proteins, a process known as apposition. Following apposition is a flattening of the myoblast membrane to increase its contact surface with the myotube. This step has been shown to require elements of the cell cytoskeletal machinery. The third step in this process is a crucial one where the myoblast membrane and the myotube surface are brought very close to each other in a condition known as ‘tight apposition’. The tight apposition forms multiple areas of cell-to-cell contacts called ‘nascent pore sites’. These contact areas form fusion pores, where the cell membranes of the myoblast and myotubes merge. The fusion pores eventually expand until the myoblast is fully incorporated into the growing myotube.

Future studies are likely to involve detailed investigations on the mechanisms of fusion pore formation and in discovering the molecular players involved in pore formation. “We believe that the cellular and molecular mechanisms uncovered in this study, and in future studies are highly conserved, and therefore also applicable in vertebrate systems. This study is therefore likely to provide key insights into understanding muscle development and repair processes”, says Dhanyasi.

The paper titled “Surface apposition and multiple cell contacts promote myoblast fusion in Drosophila flight muscles” can be accessed here.