Season 2, Episode 11: Cultural Transitions: Building a Career in American Science

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Episode Guests

Yamini Dalal, Ph.D.

Dr. Yamini Dalal became interested in chromosome structure and epigenetic gene regulation during her Baccalaureate years at St. Xavier's College, Bombay, India, where she graduated with a double major in Biochemistry and Life Sciences in 1995. She moved to the United States for her post-graduate work. In Arnold Stein's laboratory at Purdue University, she used classical chromatin biochemistry tools to understand how DNA sequence motifs and linker histones can shape the chromatin structure in silico, in vitro, and in vivo. During this time, she discovered that the regions of the mouse genome contained alternating tracts of stiff and flexible DNA, which allowed in silico prediction of nucleosome positions. These positions could be recapitulated in vitro using just purified histones and DNA, and detected in vivo, at developmentally regulated genes in mice. She also studied how linker histone H1 could influence nucleosome positioning and chromatin folding in vitro and in vivo. For these studies, she received her Ph.D. from Purdue University in 2003. Histone variants were the next logical step in teasing out how intrinsic variability in the chromatin fiber can encode a diversity of biological functions. To study this aspect of chromatin structure, Yamini moved to Seattle to work with Dr. Steven Henikoff at the Fred Hutchinson Cancer Research Center from 2003-2007. Using a range of biochemical analyses, she and colleagues uncovered that the Drosophila centromere-specific histone variant makes non-canonical nucleosomes, features of which are reminiscent of the ancestral nucleosomes seen in the archaebacteria. Recent work from her lab has shown that some of these unusual features are conserved in human cells, that centromeric nucleosomes oscillate in structure and in modifications over the cell cycle. Such oscillations are perturbed in human cancers wherein CENP-A is innately mis-regulated and occupies ectopic regions of the human genome linked to instability. Her lab has also worked on dissecting the function of transcription of repetitive loci within human centromeres. We are now expanding our studies to other histone variants in human tumors, and using machine learning approaches to disrupt cancer-specific chromatin interactions. She was awarded tenure at NIH in 2018. In 2021, Dr. Dalal became Senior Advisor for Faculty Development, CCR Office of Scientific Programs.

Sweta Sikder, Ph.D.

Dr. Sweta Sikder is currently a postdoctoral fellow at the National Cancer Institute, NIH, where her research centers on examining chromatin dynamics during the aging process. With over ten years of experience in carrying out various wet lab molecular biology techniques and a solid foundation in epigenetics and chromatin research, she brings a strong background to her work. Dr. Sikder's past academic training has equipped her with extensive knowledge in biochemistry, genetics, epigenetics, and cancer biology. During an internship at the Indian Institute of Science, Bangalore focused on prokaryotic stress gene regulation and its expression, Dr. Sikder found herself drawn into the world of chromatin and gene expression. This led to her PhD research in Jawaharlal Nehru Center for Advanced Scientific Research, Bangalore aimed at understanding the cellular functions of non-histone chromatin protein PC4 and its link to breast cancer progression particularly that in radiation resistance. Her doctoral work provided significant insights into epigenetics, chromatin biology, and autophagy resulting in several first author publications. Building upon this technical foundation she joined Dr Dalal’s group at NCI for postdoctoral studies. Here she extensively studies how centromeres are altered during aging. Her research shows how centromeric proteins and transcription is regulated as human ages. This study further uncovers novel mechanisms that can reactivate dormant centromeres in aged cells leading to their mitotic rejuvenation. Dr. Sikder seeks to deepen her scientific exploration into the epigenetic control of cellular aging and oncogenesis.

Show Notes

Yamini Dalal, Ph.D.
Sweta Sikder, Ph.D.
NCI Center for Cancer Research (CCR)
Biochemistry by Donald Voet and Judith Voet
NCI K99/R00 - Pathway to Independence Award
NCI Intramural Research Program

Ad: Interagency Oncology Task Force Fellowship (IOTF)

Your Turn Recommendations:

The Worlds I See: Curiosity, Exploration, and Discovery at the Dawn of AI by Fei-Fei Li (book)
Hear the Wind Sing by Haruki Murakami (book)
Behind Her Eyes (Netflix series)
Poor Things (movie)
The Three-Body Problem by Cixin Liu (book) & 3 Body Problem (Netflix series)
The Knowledge Machine: How Irrationality Created Modern Science by Michael Strevens (book)

Transcript

Oliver Bogler
Hello and welcome to Inside Cancer Careers, a podcast from the National Cancer Institute where we explore all the different ways people fight cancer and hear their stories. I'm your host, Oliver Bogler from NCI's Center for Cancer Training. May is Asian American and Native Hawaiian Pacific Islander Heritage Month and is dedicated to celebrating the contributions members of these communities make to the United States. One of the things I love about science is that it is an international enterprise, bringing people from all over the world together to focus on shared goals like ending cancer as we know it. As a result, many scientists leave their homes and live and work in another country. 
Today, we're talking to two scientists originally from India who have made the NCI's Intramural Research Program their scientific home. And we'll be talking to them about what it was like to come to the US to pursue their science and how it's going and their careers. Listen through to the end of the show to hear our guests make some interesting recommendations and where we invite you to take your turn.

So it's a pleasure to welcome Dr. Yamini Dalal, senior investigator in the Laboratory of Receptor Biology and Gene Expression in NCI’s Center for Cancer Research. Welcome.

Yamini Dalal
Thank you all of you.

Oliver Bogler 
Welcome also to Dr. Sweta Sikder. She is a visiting postdoctoral fellow in Dr. Yamini's research group. Welcome.

Sweta Sikder 
Thank you.

Oliver Bogler
So you both came to America during your early careers. Yamini, you came to pursue graduate work at Purdue and Sweta, you came for your postdoc at the NCI. We'll talk about your careers later, but I wanted to start by asking you what it was like to move to another country for your science.

Yamini Dalal 
All right. Well, thank you, Oliver, for hosting us on this fantastic show. I've listened to the blogs in the past and I really find it a great way to disseminate what we're doing here at the NCI and share our perspectives. I came to the US when I was, I think, 22 or 23 and I left India on Independence Day, which was sort of a bittersweet feeling. And I moved to the Midwest to pursue graduate school. And the first thing that was the biggest challenge for me was the weather because I grew up in Bombay, which is subtropical, and it's never cold. And the very first thing I discovered about the Midwest is that it gets really, really, really cold in the winter. And then in a way, I suppose that spurred my scientific studies because I didn't want to leave Lily Hall, which is nice and warm all winter round. Sweta?

Sweta Sikder
Yes, so for me, it was a very unique kind of an experience. I came to US for the first time to join Yamini’s lab as a postdoctoral fellow. And incidentally, I landed or my flight landed exactly the day before the government shut down. That is in 2020, where the whole world shut down to say. 

Yamini Dalal
On the Ides of March very appropriately.

Sweta Sikder
I just had a day to come to NIH to get registered here. And then we were all like doing the pandemic shutdown and at home. So when I was pursuing my career, there was always this thing that you should, if you are in science, you should always have that US exposure of science. But for me, when I landed finally in the US, it was a very, it was a very different kind of experience.

Things started changing slowly. But what I faced for a long time is like being in a society which is so open, but where you cannot really access people because of the pandemic shutdown. So now I'm more glad that we have like a very vibrant campus. We meet lots of people and, but it was all not accessible when I came to US.

Oliver Bogler
So making a connection with people that may be at the same career stage as you are, and maybe who have some shared background, maybe also coming from the country you were coming from, is that an important element? And obviously, the pandemic made that super hard, right?

Sweta Sikder
Yes, and also when I came to US, I had this open kind of a, I wanted to have an open mind and wanted to get an exposure of other culture, the other society as well. Obviously, you want people coming from the same country like me from India, you want to connect with them and then share your things, but I wanted to have a different kind of an experience. I wanted to mix, see other people, talk to them, have kind of a unique experience, which was kind of difficult. We all met through Zooms and online meetings. And even when we used to see people, when I used to go around for a walk or something, I used to see people walking, but we all maintained that social distancing thing. And it was super, super difficult at that point of time, but now looking back, I feel that it kind of mentored me that the pandemic time when we were all shut down, it also helped me in my inner and my personal growth as well. 

Yamini Dalal
I think there's a resilience, right, that we had to reach into during the pandemic. And I think you did a really great job reaching inside yourself to survive those first six months completely alone.

Sweta Sikder
Yes, and also at this point, I would like to mention this, that this lab was super helpful, like all of my lab colleagues, because I haven't met them ever. Like it was the first time meeting them, but they were very, very helpful reaching out because when I came for the first time, I had to figure out like many logistic things, right? Like doing your social security number, having a bank account, like all those minute things.
But I'm grateful in the sense that I got very supportive colleagues, my mentor, Yamini here. And they were always like a text away to help me at any time despite the pandemic.

Oliver Bogler
You mentioned also that I guess the United States is kind of a draw for scientists from across the world. And that's certainly been true over the last many decades. Um, tell me more about that. What, what specifically were you both, uh, hoping to accomplish by moving to the United States?

Yamini Dalal
Yeah, I think, you know, my feeling, Oliver, was when I was growing up in Bombay, I grew up in a very specific, very privileged class of people that all had similar exposures. And it really comes down to, I had no exposure to people that were outside of that little bubble. And we all went to really great schools. Our parents were professionals with advanced degrees. You know, we got exposed to like the best science, the best art, but it was all in this bubble of not knowing really even anything about India when I was growing up. I felt like I didn't know what it meant to be really Indian. I knew what it meant to be a Bombayite, in South Bombay, which is sort of like Manhattan, but I didn't know what it really meant to be from a different social class or from a different culture from what I had been exposed to. 
The beautiful thing about going to Purdue, especially, was that it's an extremely international school. I still have friends I've made there from all over the world. They're faculty now in New Zealand and Australia and England and Europe. And I had friends from Gary, Indiana and Montana. Places I had never heard of, maybe I read about them in books. And because Peru had a great ecology department, many of my friends were actually people in their 30s who were coming back to grad school after having worked for a decade in really low paying jobs, principally because they had undergraduate debt, a concept to which I had never been exposed. Because in India, you don't have undergraduate debt. You don't have no debt at all. Indians don't usually, they don't embrace the concept of debt because schooling is generally much, much more affordable there, even the best schools.

The biggest shock to me was to find out most of my friends had thousands of dollars in debt. And as a consequence, they had to wait almost a decade to come back to grad school, which means they took it very, very seriously. It was very different for someone like me who'd just been on this kind of trajectory this whole time. So I got exposed to the poverty, the idea that poverty can really alter your scientific trajectory very significantly and that you've got to be given an opportunity.
And this is where Purdue really excelled because they had RA ships, research assistantships and TA ships that funded almost everybody. Nobody really had to pay for grad school. Of course you had to work really hard. I spent 20 hours a week as a TA. I thought that experience was absolutely transformative. I'd never taught before in a formal setting. To teach 20 hours a week to people from the Midwest, because most of the undergraduates were actually from the Midwest, I had to slow down my speech by at least tenfold, which actually taught me the importance of making jokes when you teach to just sort of get a break, a lull in the discourse, because people are really trying, struggling to keep up with you. And you're operating at this level of information and they're here and you've got to find a way to make that accessible. I found the Purdue teaching experience changed the way that I thought of science as an enterprise in which you have to bring somebody along because they're going to have better ideas than you.
And because the teachers at Purdue, one of whom just passed away, Joann Otto, were brilliant, I learned a lot from these educators. They'd spend their whole lives teaching in addition to doing science, which is again a concept I hadn't been exposed to before. These experiences with teaching in a national setting, learning how to make things accessible rather than holding the information in for yourself, I think it changed the way that I perceive my job as a scientist.

Sweta Sikder
Yes, for me, it was like a slightly different. I came at a much after finishing my grad school. So I initially always wanted to do my PhD from abroad. Somehow it did not work out at that time. I just sat for an exam, which is like super competitive in India, which is which you need to, to get through to grad school. And when I went there, I had no expectation that I will qualify in the first round because usually like 95 % of people don't get through that. So eventually grad school happened in India, but I always had this thing of going especially to US because I used to hear a lot of interview talks from scientists, US scientists, Nobel laureates. And some used to visit India and I used to interact with them a lot. So all these things made me think that my full growth as a scientist or as a person will not be complete unless I go to US. I mean, it was kind of a childish dream which I had during my bachelor's that my career path will not be complete until I reach US. 
But coming here, I think it's nothing like that. You grow constantly. You grow all the time. Wherever you are, it doesn't matter. The passion of science should drive you in your career. But yes, in science, I would say that the way we do science here, the way we pursue a question, how to solve it and the curiosity driven science. Like you're curious about a simple thing and you ask that question and you try to find out that answer. So that actually drew me to US. But I would also mention that the training which I got in India was very good. We had like hands -on training, very good course in my bachelor's, master's, and then when I went to grad school. And also like all the experiments, technical skills, I kind of enjoyed that part of my career as well.

Oliver Bogler
So the United States, the science here has the reputation of being like you just said, Sweta a curiosity driven and kind of an idea meritocracy in the sense that the best ideas prevail. And so that's its reputation. Was that your experiences when you both came here?

Yamini Dalal
Yeah, absolutely for me. My thesis advisor, Arnie Stein and I had this ongoing conversation for like five years where we constantly challenge each other with hypotheses and ideas. And he never made it feel like, you know, he's one of the people that started the chromatin field. He trained at the NIH actually, many years ago with Bob Simpson. He never made me feel like I was lesser than him. The only difference between was experience. He had more experience and he was willing to share it.

But he was always excited to hear my ideas. And, you know, we had a little hypothesis book with like thousands and thousands of ideas that we wrote over five years. Our relationship really defined my science because he made me realize just how much fun American science can be because there's this equal footing in the empire of the mind. And when I was coming from India, I felt like back then, now it's not true, but back then India was still very hierarchical in its science. You had the chair, you had the professor, they knew more, you had to be very very respectful, which I think is still important. I think it's important to be respectful. But here I feel like there was an emphasis on challenging ideas and challenging dogma. And that made it very creative, but it also made it really fun. 
The fun aspect of science was something I think I truly embraced after coming to Purdue. And also the exposure to people doing just all kinds of science. People working on the smallest microplankton, people working at Purdue on space. I used to go to lectures on physics, gravitational stuff, because Arnie used to be a physicist, so he'd always encouraged me to learn about physics. I had friends working on all kinds of problems, you know, the sexual development of ferns, first species ever to have gametophytes. So these friends really defined my approach to science, which is fun and curiosity driven. And I think that is still the strength of the United States. But other countries have now embraced that principle. And I think it's made science really very strong in India, in Germany and other countries where many of our people who were trained here went back home and are now chairs of departments and very senior in their leadership.

Sweta Sikder 
Yes, I also agree to some of Yamini's points. When I joined this lab, actually, I wanted to work in aging, but I wanted to work in epigenetics, chromatin, and that's how I met Yamini. Actually, I met Yamini through another professor who is another chromatin biologist. So he actually recommended me to Yamini.
And we had this long conversations in how to address a simple question of biology, like how do our chromosomes behave when we age? And although we went through a lot of challenges because aging itself is kind of challenging in terms of how you ask the question, what kind of tools you have, what kind of system you want to look into, but I have thoroughly enjoyed this journey for the last three to four years. We go back and forth with the simple question and then find out ways how to defy our hypothesis and then come up with results which is in lieu with our hypothesis. So this is kind of fun. 

Also the exposure of the branch as well, like other scientists, other colleagues, other postdocs. I like this environment of NIH especially, especially of the branch where we can just walk around, talk to other fellow postdocs who are doing like cool microscopy techniques, single resolution microscopy, high throughput imaging, and just have a conversation over a cup of coffee. And everyone is like very eager to help you, give you insights, which I think should be a more in the system in India, especially I would say, because we need more of a congenial environment where we can boost each other's science. And that, I think, helps scientists overall.

Oliver Bogler
So at the heart of the science that you're describing, under ideal circumstances, is a, as you said, an open discourse and a sort of slightly rough and tumble exchange of ideas and competing the ideas are competing. To create that atmosphere in a research team, particularly one that has members coming from many different cultures, is a challenge. It's not easy. I mean, we think of ourselves as scientists as sort of being above culture, but it's not true. We're cultural beings like every human. Yamini, as you manage your research team and lead your research team, how do you accomplish that?

Yamini Dalal
You know, as I said, Oliver, I had two fantastic mentors, Arnie Stein at Purdue and Steve Henikoff at the Hutch. The thing that unified both Steve and Arnie was a fundamental, absolute love for science. And that love for science transcended rank. It transcended funding. It transcended who you were, the privileges you came with. You could argue with Steve or Arnie any day about a hypothesis and they didn't care. You know, it would get loud, it would get fractious. But it was all in this intellectual sphere of, hey, let's figure this out. This is going to be fun. I tried to bring that level of fun and intensity to my lab. I'm naturally very intense. I tried to lower my intensity. I think that was maybe the big thing I had to learn was how to titrate myself, my own personality, so that I wasn't overwhelming people in the lab. I have not really succeeded, I think, but I try.
So part of that was learning that it didn't matter who the smartest person in the room was because sometimes the best ideas did not come from who thought they were smartest. Intuition has a very, very big role in science and some of the best ideas we've had in the lab have just intuitively arisen in lab meeting. When we're just throwing an idea back and forth, I'll give you one example. Song Fu was our first summer intern. He's a resident physician at Yale. And when he joined my lab from the University of Maryland, he came for three summers in a row and then stayed as a post-bac. And he got really intrigued by this finding that Rajbir Gill had made, who was my first lab biologist, that all the extra centromeric protein that was being expressed in cancer cells was going outside centromeres. And Song said, hey, maybe it's making these fragile sites because it's making the DNA more open. And, you know, we thought about that idea, but we never formalized it.
And he got so excited by his own idea, he tested it and that became a thing. It became a field. What he discovered became a field. And now, you know, many, many people have worked on it since one of the best people in my field, Genevieve Almouzni, co-discovered it at the same time as we did. And those papers came out like a few months apart. I think that is the power of allowing people to feel comfortable and encouraging them, urging them to speak up in lab meeting. So we go around the lab.
And we're like, what do you think? What do you think? What do you think? Some people find that very uncomfortable actually, Oliver, because people don't like to be put on the spot right away. But I feel like that level of discourse is essential for the lab to function as a team, as opposed to me saying, these are my ideas.  

Oliver Bogler
I was gonna say when someone is uncomfortable in that setting, how do you make them more comfortable or how do you encourage them to step outside their comfort zone?

Yamini Dalal
Yeah, I think part of it is just exposure. The more they see others in the lab doing it, the more comfortable they get. We are also generally very small lab. We've never had more than seven or eight people. Our usual number is six. So it's pretty cozy. We're sitting in a small conference room. It's not like 25 people sitting on a large conference table. And that I think makes it a little bit more comfortable because people don't feel as exposed to give their best ideas up. I also have this challenge that I always throw to people in my lab and it's an ongoing joke. Prove me wrong.
My best day is when somebody takes my best idea, what I think is my best idea, and then just totally shows I'm wrong. So I think that kind of humorous challenge to the lab lets people know it's okay to fail and it's okay to be wrong. In fact, it's more than okay to be wrong because that's how we figure things out. So I like to think that approach has worked because if I'm wrong, they know it's okay for them to be wrong. And Sweta can correct me on whether that's a good strategy or a bad one. But it's a strategy I use all the time because I think it's true.
You're never going to be right all the time. It's inevitable you're going to be wrong, but it's fun to use what you've learned from being wrong to educate you on what is actually the truth of the biology.

Sweta Sikder
Yes, I will pick up that thing from where Yamini says that to challenge her and show that she's wrong in her idea. I think that kind of environment or that kind of setting helps you to inculcate more of your scientific abilities because you are under no pressure to showcase something. You are just driven by your curiosity and by your scientific skills, and then you can report anything, whatever you get, whatever your observations are. We, as Yamini mentioned, we are a small group, but we are very intertwined and interconnected. So it's all the time we are talking to each other across our lab tables. We are having conversations of crazy ideas, which even Yamini doesn't know. 
And then sometimes the experiments work. And then we come up with results and we discuss that in our lab meetings. So, I think this kind of a congenial environment helps you a lot. And also, I am really happy that here in Yamini's lab, we regularly do extramural activities. It's kind of a must. We go for runs, marathon runs. We go for kayaking.

Yamini Dalal
I don't go for the marathon runs …  this is the rest. Yeah, that's not me. The lab hike is my thing, but the rest is all the lab.

Sweta Sikder
Yes, the kayaking, lab hiking. So this kind of friendly environment helps you a lot. It helped me a lot because especially coming from a different background, different kind of a cultural society altogether. And then blending into this society, this activities actually helped me, gave me a lot of exposure of how people lead their lives. And it helped me a lot.

Oliver Bogler
Reminds me kind of of a startup vibe, right? Like a small company startup, where it's not just people you're working with, you're also spending some time with them. It's a more intense and more deeper relationship. So yeah, very interesting. All right, we're going to take a quick break. And when we come back, we'll talk to our guests about their careers and their science. 

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Oliver Bogler
All right, we are back. Yamini, let's start with you. When did you realize you wanted a career in science?

Yamini Dalal
So I grew up in a medical family and this has been, I've written about it in various editorials. I was always exposed to science since I was a child. My father was a neurologist, my mom's a physician. We have many people in the family who are doctors. And the general understanding was in India, especially in the 1980s when I was growing up, giving away my age here, there were only a few ways to white collar success if you weren’t a business family. So even though we had lots of friends who were business folk in South Bombay, which is very privileged and wealthy. The rest of our friends are all white -collar professionals, doctors, lawyers. And the only way up, you know, you're competing with millions of other humans who are extremely intelligent. The only way up was to excel in something. 
I was really, really always very good with biology and writing, English literature. I really loved writing and reading, but I actually wanted to be an archeologist. When I was eight, I don't know, four or five, maybe seven, I don't remember, I had this little Time Life series book on the Indus Valley and Egypt, ancient civilizations, actually I still have it. And I was obsessed with the Indus Valley code, which is on these ancient seals from Mesopotamia that were also in the Indus Valley in India. And nobody has decoded and encrypt this script, nobody knows what these seals are saying, there are thousands of them. And I wanted to be the person that was going to decrypt these. And my dad was like, well, that's not a profession. You're not going to make any money. You’ll be digging, you know, in the sand for 10, 20 years. You'll never find anything. So why don't you focus on your biology? And, you know, we actually ended up having a pretty big fight before I went to college because I really thought archeology was going to be my thing. And then biology could be my second thing. I was good at both, but I really wanted to do that. 
But luckily I got into Xavier's, which is a private university that was started by German Jesuits in the 18th century, in the 1850s. And Xaviers has a fantastic combination of art, history, culture, and science, very rare for Indian college. Most Indian colleges, either it's science or it's technology or engineering, and then there's art and the things don't mix. Xaviers was one of the few places where you could actually do all of it. So even though I was in biochemistry and life sciences, which I loved, I mean, absolutely loved my experience at Xaviers, it was fantastic, I could go listen to lectures on archeology and history so I could maintain it as an outside passion. Which helped me, I think, stay healthy in my interests, not be completely obsessed with one thing, which was chromatin. But at Xavier's, I listened to a biochemistry lecture and the professor showed an electron micrograph of chromatin, which I'd never seen before. Despite all the medical books my dad had, I'd never seen an actual photograph with the first electron micrographs of chromatin, which were published in 1974, which happens to be the year that I was born. And these images were from Chris Woodcock, who I got to know later in life when I was at Purdue, because he came to visit. And it just blew me away that these little beads on the DNA in all eukaryotes, whether you are a pea or a human or a whale or a yeast, we have the same chromatin structure, but we're completely different. 
And then after the Human Genome Project, you know, we have basically the same number of genes as a worm. And yet we're fundamentally different, right? So that the epigenetics, the stuff that's above the DNA controlling development, controlling fate, controlling disease was just fascinating to me. And that, I think that just made me fall in love with chromatin and I haven't fallen out of love and it's been now 20 plus years. So I think it's fair to say this is gonna be a lifetime obsession.

Oliver Bogler
Okay, very interesting, very interesting. Sweta, how about you? Why did you choose biology as your path?

Sweta Sikder
So yeah, that's kind of interesting, which makes me think that why I really came into biology. I was always a curious kid and like I used to read a lot of crime stories and detective stories and all that with doing with the forensics. So I actually wanted to get go into forensic department, like learn how to extract DNA and then find out your … the criminal who has done that. 
 I will refer to Yamini's comments here, that when you grow up in India, the society kind of conditions you, like you either have to take up engineering or medical to have a successful career. But I was I was lucky in the sense that my parents were actually very encouraging. They asked me to pursue whatever I liked, which is kind of very uncommon, I would say, like in an Indian setting. They asked me that whatever you're passionate about, just do that. And then I actually wanted to become a biotechnology forensic expert. So I took up microbiology in, I was in, I went to Calcutta in Lady Brabourne College, which is quite a traditional college there for women. And I took up microbiology as, and there I read a lot of books, like one of them was by Daniel [Donald] Voet and Judith Voet, Voet and Voet, biochemistry book. And I was like fascinated by the cover page and like how the microscopic images of like proteins, DNA. And that's how this interest inculcated in me. 
But then I took up biotechnology later for my masters. And it was during my masters, in my master's school that actually my teachers or professors who used to teach me like inculcated this interest in me to pursue science, like doing basic science. And I am kind of grateful to them because it's kind of, you know, each of your mentors shapes your career at different stages of your career path. So I'm kind of lucky to get mentors who along this path have helped me to understand my passion and shaped my career path.
So then I, as I said that I qualified for the PhD exam and then I went to grad school to Bangalore, which is like a hub of science for in India. You have the Indian Institute of Science, Jawaharlal Nehru Centre where I did my PhD. And it was a great experience for me, like doing science in India, I would say Bangalore is the best place to do.

Oliver Bogler
So what drew you to work on chromatin specifically? Yamini already explained her impression of that photograph that she saw. Was it the same thing then, Sweta? You also saw images of DNA and that made you want to work on the structure?

Sweta Sikder
Yes, I mean, I did see a lot of like that time sequencing the sequencing thing, the era was coming on and you can sequence your whole genome. And that kind of drew me into unraveling what is in our genome and what actually our chromatin or our genome is made of. So in that way, that kind of … it helped me raise my curiosity. But then when I went for my grad school, I worked extensively in chromatin and especially in the cancer context and in radiation resistance, breast cancer models. And that actually raised or inculcated this passion for chromatin. And I think maybe I'm tied to my whole life now to it.

Oliver Bogler
Also a lifetime passion. Yamini, so I understand that your research program focuses a lot on centromeres. Tell us a little bit about that and what are the key things you're working on with your team?

Yamini Dalal
Right. So centromeres are special loci of chromosomes that are involved in chromosome segregation. So it's where the microtubules bind. So they're fundamental. They're essential. If you knock out any major component of the centromere, you're dead. It doesn't matter what species you are. All eukaryotes have centromeric components that help to segregate the genome faithfully. And this has to happen thousands and thousands and thousands of times over the course of the lifetime of an individual in thousands and thousands of cells.
And in any one of those cells, if it goes wrong, you get one chromosome less, you get one chromosome more. That's called aneuploidy, which is strongly correlated with disease. So it turns out that centromeres are defined by a very special histone, which is a protein that is part of the chromatin. And that histone variant is called centromeric protein A or centromeric histone H3. This particular histone is essential if you knock it out, you're dead because it forms the basis of the centromere.
When I actually started working on chromatin in grad school, and I was not interested in centromeres at all, I was working on nucleosome positioning, you know, how do the genes, how do the nucleosomes that are the beads that are on those DNA fragments, how to get shoved aside so that RNA polymerase can read a gene and stuff like that. Steve Henikoff came to give a talk at Purdue when I was a grad student, and my job was to take him between buildings. That's what you did as a senior grad student in the winter, especially where nobody else wanted to do it. That was your job. It was great because you got to talk to all these leaders in the field. And Steve had just discovered with Harmit Malik that centromeric histones, despite being essential, are fast evolving. It made no sense. This was called the centromere paradox. Despite the fact that centromeres are essential in every species in which they exist, both the centromeric DNA sequence and these proteins that are essential for life are fast evolving. So if you compare a yeast centromeric protein to yours or mine, they're not identical.
And now with nanopore sequencing, we know that centromeric DNA amongst individuals is actually not identical. It's fast evolving as well. So biochemically, this just became like this fantastic epigenetics problem. How would these fast evolving proteins and the fast evolving DNA, do you make the same mechanical structure that pulls, helps to pull chromosomes apart every cell cycle in every species? Because microtubules are conserved. They look exactly the same in every organism. And when we look at chromosomes, they look the same in every organism, but the centromere structure, despite being the same, is dictated by these proteins that are not the same. 
I found this to be just such a fantastic puzzle. And even though Steve frightened the bejesus out of me, because he's a very intimidating personality, he's extremely intense, I thought I have to go work with him, because he's going to challenge me. And he did. But I'd like to say I challenged him too, and he will acknowledge that.
So working with Steve on Centermiers, I had the freedom to pursue pretty much anything I wanted. Steve's motto in the lab was, I will give you as much rope as you need to hang yourself. Which at the time, I have to say now we’d never say stuff like that, but it made sense. And his goal was to give you the freedom you needed to pursue your crazy ideas and project. And his job was just to make sure that you didn't completely go off the rails. It was a very difficult project. It was very challenging, but I had a blast.
And that continued then in my lab, we decided to look at why centromeric proteins are overexpressed in cancer. I wrote a K99 when I was still in Steve's lab, which is a funding mechanism. That was the first, I think the first generation of K99 grants in 2003, sorry, in 2007, I think. And what I covered in the grant was centromeric proteins are overexpressed in virtually every solid cancer. And everybody was citing those papers in the grants, but nobody, nobody at that point had looked into why these proteins are of overexpressed, what happens? Because it's obvious that if you have too much of this protein, something bad would happen. That was the basis of my lab and that's why I got hired at the NCI. I didn't get funded by K99, which is also NCI extramural, but I got hired by NCI intramural, which is a better deal, I think, because they funded me for 16 years to figure this out.

Oliver Bogler
Well, that's a perfect segue to my next question, which is, you know, the NCI intramural research program is a little bit different from your typical research institute or university, right? So I wonder what drew you then to that program, Yamini, to bring your research to the NCI, to the Center for Cancer Research.

Yamini Dalal
Yeah, Oliver, that's a great question. When I interviewed for faculty positions, you know, there's some really exciting schools with lots of opportunities to be completely independent and to carry my research forward. What I loved about the NCI and the NIH actually, not just the NCI, was the people I met here. I felt right at home. And I know that sounds odd because when I came to interview here in 2007 or 2008, there were barely any Indian women PIs.

In fact, all the people I met were leaders in my field. I'd read about them in textbooks who had that faculty interview with me or were like, you know, 10, 20 or 30 years older than me. They had all this magnificent chromatin experience, but it was like walking into the library of Alexandria. I felt like I could tap into all their brains and get all this information on chromatin that they had discovered themselves. And that would help me in my program. And I really felt like right at home. It was really strange because at the time I was like only 33 or 34. These people are all like National Academy. They're very famous. But I felt right at home in this sort of group of scholars. So fundamentally what drew me to the NCI was the people that I met during my faculty interview. I felt right at home. They were not at all intimidating. They wanted to know what I thought about their program and their projects. 
I think that is the uniqueness of the NIH because we're not funded by grants in the same way that extramural is. I think the interactions you have are very, very collegial because there's no competition inside the NCI for the same program. And as a consequence, people are just used to giving you information completely unsolicited. They're happy to do it. They're happy to give you tools, technology, ideas, and support. And I experienced all of those things as a tenure track investigator here. That's what drew me here. And that's what keeps me here.

Oliver Bogler
Sweta, you were nodding as Yamini was describing the environment. I wonder what it's like when you come into this environment as a postdoc. What are your experiences?

Sweta Sikder
Yes, so actually I will start this from a very early experience when I joined NCI, Yamini's lab. So when I was interviewing with Yamini, I came up with this idea that we should look at aging and senescence. And she said that it's a very cool idea. And I was like, very flattered because you meet scientists and whose papers you have been reading centromeres. And then if that scientist tells you that you have a cool idea. It really boosts you a lot. And I'm happy to say and share that I'm getting this encouragement throughout. It's not only in the branch, but when I give talk at a Chromatin Forum at NCI and outside NIH, I constantly get supportive comments and suggestions, even not only on science, but as a career altogether. It can be from a very new tenure track faculty or a fellow postdoc. 
All those things, I think, helps you a lot. And I would also mention that the peer-to-peer mentoring actually has shaped a lot of my decisions throughout my career path. And it is helping me a lot. So yes, it has helped me. And we do get a lot of help in terms of scientific, career-wise, throughout NIH.

Oliver Bogler
Yamini, you wear another hat in addition to being a senior investigator, you're also the senior advisor for faculty development in the Center for Cancer Research. Can you tell us what that role is about?

Yamini Dalal
Yeah. So Oliver, a few years ago when we had the pandemic, I had this sort of existential crisis because I realized when you're not being a lab PI, right, and you couldn't meet the people you're working with intimately every day, you're not really directing their research because we couldn't even come to the lab. And we were the NIH was probably the last to open up its doors completely. I think we were like partially shut down for more than a year, way past even vaccination. I felt like what is my role? What good am I doing for our society?
And I think it just made me really worried that I wasn't maximizing my ability to do something good outside of my own lab. I've always been very interested in the work outside of my own lab. I have a lot of scientific passions. I listen to talks all the time. And one of the things that came up during these chats with people during the pandemic first year was that they felt there wasn't a lot of support for tenure tracks. 
And I remember when I was a tenure track, I had just crazy support from all my colleagues here because it was open, you could meet people, you get to know them. So I felt like this is something I could do. So I approached our scientific director of the time, Tom Misteli, who's also a colleague in the branch, he knows me really well. And I said, you know, I really want to do something and I think I could do something like this. And I have to say him and Bev Mock, who was the director of the scientific programs office in CCR were very supportive and they created a position that did not exist yet at the NIH, at least not at NCI.

And as a consequence of me taking on that role and being sort of an advocate for tenure tracks, being an advisor for them, I read site visit documents. If they can't find something, I help them find it. The great thing about having been at the NIH for 16 years and being a friendly person is you know a lot of people across many institutes. And over the years, I've been lucky to make friends across various programs, various departments. I even knew for a while the chief of police because one of my undergrad grad students needed help after a little fracas with the NIH safety people. So I got to know a lot of people and I thought this is something I could do. I could facilitate interactions. And I'd say that's maybe the major goal as a faculty advisor is to help people find answers that they were struggling to find. They already have beautiful science, so the help is not scientific. It's really more how do I find this? Who does this? How do I get this? Who do I talk to I want to do this? 

And I think during the pandemic, it was hard to find those resources because you couldn't just walk down the hallway. So I guess I became that hallway and it's been extraordinarily rewarding.

Oliver Bogler
Yeah, that kind of implicit information can be vital to survival and success. That's very interesting.

Yamini Dalal
Absolutely. And I want to say every Chief that I've talked to has really embraced this idea of having a faculty advisor. They didn't view it as competing with their domain or their sphere. And that's the other beauty of the NIH. There's not a lot of ego about this. They were like, yeah, if you can help, help. Do what it takes. So I want to really give a shout out to all the Chiefs who supported this notion of a faculty advisor, because after we have it, we instituted a faculty advisor, most of the institutes across the NIH decided to take on an equivalent position.
It's also a nice way to learn a little bit about leadership, because it's easy when you're not in leadership to blame them for everything that goes wrong. It's not until you start talking to leadership that you realize their job is actually very, very complicated and very challenging. So being an intermediary, which by the way, the word Dalal, the meaning of the word Dalal is intermediary, a facilitator. The Dalals are traditionally traders in Gujarat. So I thought it was very fitting, first leadership position for me.

Oliver Bogler
It's fate. 

Yamini Dalal 
Yeah.

Oliver Bogler
So Sweta, what advice would you give to someone who might be in the latter part of their undergraduate career, maybe in another country, thinking about cancer research in the United States, maybe even at NCI, what would you say to them?

Sweta Sikder
Yeah, I would like what I have understood is that you should first recognize your interest or your passion, especially the field which you want to work on. My PhD mentor Tapas [Kundu] used to say, ask big questions   and then find out small answers, like small techniques to answer those big questions. And so I would also echo that and say that one should establish, and once they know that this is the kind of science they want to do, just to reach out to anyone. I know that coming from India, we have this kind of a barrier, I would say,  that we think a lot that whether we should reach out to a Nobel laureate or just write an email, how will that be perceived? I would say that nothing. Just if you want to reach out to someone, just reach out to someone. 

Oliver Bogler 
And Sweta, do you already have a next step in mind? Obviously a postdoc is by nature a defined phase in your career.

Sweta Sikder 
Yes, I see Yamini smiling because I think we talk, we are now having regular talks on this. But yes, of course, when, I think before I joined postdoc or within a year, I knew that I always had this passion of doing academic kind of science, like science doing in an academic environment, pursuing your own question.
So yes, I have, I want to ask more questions of how the chromatin behaves during aging. And I am planning to pursue this career. So yes, we have a timeline set up in mind, some plans on how to go about and keeping my fingers crossed for it.

Oliver Bogler
Great. Yeah. Well, I wish you all the success with that next step. Yamini, last question to you. What advice are you giving the early career investigators, the grad students, the postdocs, the postbacs in your lab and around your branch and NCI? What advice are you giving them?

Yamini Dalal
Be happy. I think that's really my fundamental advice. If you're not happy doing what you're doing and it isn't an all-consuming passion for you, then there's no reason to do it. Because those are the only reasons to be unhappy. If you're just obsessed with something so you can put up with pain, then do it. Because you can't think of anything else that's going to make you happy. But if something isn't working out for you, find something else. Find somebody else. And there's no shame in that whatsoever. In fact, you'd be doing yourself and other people a favor if it's not working out that you find an alternative. 
 My motto always has been, and I think that's just true in life, is you find something that really engages you and motivates you. And if you can do that, then all the external support is just a cherry on the top, but everything else is yours. You built it yourself. And there's a great deal of pride in that kind of accomplishment.

[music]
 
Oliver Bogler
Now it's time for a segment we call your turn because it's a chance for our listeners to send in a recommendation that they would like to share. If you're listening, then you're invited to take your turn. Send us a tip for a book, a video, a podcast or a talk that you found inspirational or amusing or interesting. You can send those to us at nciicc@nih.gov. Record a voice memo and send it along. We may just play it in an upcoming episode. Now I'd like to invite our guests to take their turn. Let's start with you, Yamini.

Yamini Dalal
So I read a lot. Some of the things I read are probably not appropriate to share. But I like to challenge myself. And I've been obsessed with the worry that artificial intelligence is going to take over our lives. My spouse is an expert on machine learning and knows a lot about this topic. And in order to educate me, he gave me a book by one of the foremost women scientists in AI, Fei-Fei Li and the book is called The Worlds I See. So I've started reading it and I highly recommend it because it's a biography about her life and how she got to this point where she is the leading voice for AI, for artificial intelligence, all kinds of applications, but also a leading cautionary voice on the strengths and weaknesses of AI. I found this book really great. I'm still reading it and I'm not sure by the end if I'm going to believe that AI is gonna take over the world or not, but I do know that AI is gonna be a big part of NCI's goals going forward in trying to do cancer therapeutics. So I think it's a worthwhile book to read.

Oliver Bogler
Thank you, that's a great recommendation. Sweta?

Sweta Sikder
Yes, so I have actually a book recommendation and also a series. So I also read a lot and reading is one of my passion. So I have I am one of my favorite authors is Murakami. And recently I have read a book of him, which is interesting because it is two books, but in the same cover. And if you read from the opposite covers, you're actually reading two different books. So the book name is Hear the Wind Sing from one side and the other side is the Pinball. And if people really like Murakami's style of writing, I would recommend this as a very good read, although this was written in one of his earlier years. He, of course, has written much better books than this, but I found this is quite good.

I also have, I also see a lot of series and movies when my experiment fails, of course. But this web series, I think it streams on Netflix and it's actually a British web series, but it's called Behind Her Eyes. And it's really interesting because it kind of talks about astral projection and all, which I found is really interesting. And a movie which I saw recently is Poor Things. I think it is like an Oscar nominated one. And it's really cool, especially for biology enthusiast because it has all those, a child's brain fit on to an adult's. So it's kind of...

Yamini Dalal
It was quite disturbing actually. So my recommendation for a Netflix show that was a book I tried to read 10, I don't know, five or six years ago, The Three-Body Problem. President Obama had recommended that book as the best sci -fi book ever written. And so I bought it and I couldn't read it. It was like just dense and impenetrable. But Netflix has made a really great adaptation of The Three -Body Problem, which I enjoyed greatly. So if you're into sci-fi and physics especially, I would recommend the three-body problem.

Oliver Bogler
Yeah, that was a, I had the same experience with the book. I forced myself through the entire trilogy. Um, but the, the show is so much more approachable. Um, but, um, those are great recommendations. We're going to add, uh, put links in our show notes for people to find them. 
I'd like to make one as well. It's also for a book. It's called the Knowledge Machine by Michael Strevens. Dr. Strevens is also someone who came to the U S to do his work in his case. He came from New Zealand. He's a professor of philosophy at New York University. And in this book, he presents a unifying view of how science is done, building on previous ideas from Popper and Kuhn and others. In Streven's view, at the heart of the machine that has generated knowledge and understanding of the world over the last few hundred years is a shared notion of explanatory power and a requirement that scientific argument appeal only to the outcomes of empirical tests. Under this very powerful scheme, which he calls the Iron Rule, a narrow focus on objective scientific argument is created and it requires us to leave other considerations aside, very human considerations, for example, the aesthetic appeal of a theory. A good example comes from physics, where quantum mechanics has great power to explain the behavior of elemental particles but is not necessarily something that people can easily understand. Streven's reasons convincingly that this shedding of other considerations is what started the scientific revolution and explains why it took so long to arrive.
I think the book's a really interesting read and I'm going to admit that I came across it through my own learning about night science with my thanks to Itai Yanai and Martin Lercher, the guests on our previous episode. And there's a strong connection between this book and night science and those ideas. 

So with that, let me thank you both, Yamini and Sweta for joining me today. Really appreciate you spending time and sharing your experiences and your insights.

Yamini Dalal
Thank you, Oliver, for this lovely opportunity.

Sweta Sikder
Yeah, thank you. It was fun.

Oliver Bogler
That’s all we have time for on today’s episode of Inside Cancer Careers! Thank you for joining us and thank you to our guests.
We want to hear from you – your stories, your ideas and your feedback are welcome. And you are invited to take your turn and make a recommendation to share with our listeners. You can reach us at NCIICC@nih.gov.
Inside Cancer Careers is a collaboration between NCI’s Office of Communications and Public Liaison and the Center for Cancer Training. It is produced by Angela Jones and Astrid Masfar.
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