Biophysical Society Bulletin | April 2020

Biophysicist in Profile

Yamini Dalal Areas of Research Chromatin structure and epigenetics

Institution National Cancer Institute, NIH

At-a-Glance

Yamini Dalal was raised in a family of physicians and teachers who exposed her to science very early on. “As a kid, I devoured Michael Crichton novels, Scientific American , the British Encyclopedia , and my father’s copy of Harrison’s Principles of Internal Medicine , especially the chapter on disor- ders caused by chromosomal abnormalities,” she shares. “I’ve always wanted to know how things work at the deepest possible level. The crave to understand mechanism led me to my recent interest in using biophysical tools to complement biochemical skills that I acquired in graduate school.”

Yamini Dalal

Yamini Dalal ’s father was a neurologist and professor, her mother is a general physician, an aunt is a gynecologist and professor, and another aunt was a high school teacher. Dalal herself developed an interest in her area of specialization, chromatin structure and epigenetics, very early on in her ed- ucation, and as she learned more, her curiosity only grew. “A chapter on chromosome abnormalities in the book Harrison’s Principles of Internal Medicine caught my imagination when I was very young, maybe 12 or 13,” she says. She attended a lecture on chromosome structure as an undergraduate at St. Xavier’s University, and she was further drawn in. “The first time I saw an electron microscopy image of chromatin, I was hooked forever. I wanted to figure out how these tiny little 10-nanometer beads dictate the astonishing beauty and diversity in complex life forms all around us. Even now, in the lab, I get a thrill from seeing chromatin.” She picked up a few skills as a high school student that have served her well since —Dalal’s earliest job was grading math and English exams for her aunt, and she tutored other students in school who were struggling to keep up. “It was a great experience, figuring out ways to fully understand some- thing well enough to explain it others,” she says. “It held me in good stead when I was a graduate teaching assistant.” She attended Greenlawns High School, which follows the challenging Indian Certificate of Secondary Education cur- riculum, then went on to pursue her bachelor’s degree in biochemistry and life sciences at St. Xavier’s University, one of the oldest colleges under the University of Bombay umbrella. After completing her degree in 1995, she moved to the United States to undertake PhD studies at Purdue University in the lab of Arnold Stein . There, she used classical chromatin bio- chemistry tools to understand how DNA sequence motifs and linker histones can shape the chromatin structure in silico, in vitro, and in vivo. Dalal moved to the Fred Hutchinson Cancer Research Center for a postdoctoral fellowship in 2003. There she worked on

chromatin and centromeres with Steve Henikoff , after meeting him at a Keystone Conference. “What I remember though is not the meeting itself but spending time chatting with her while waiting for our flights at the airport. Yamini was keen to know more about centromeres, their special chromatin and the interesting way that they evolved, and I was interested in her chromatin biochemistry perspective,” Henikoff shares. “Yamini joined my lab as a postdoc and got her start in the centromere field while complementing her biochemistry ex- pertise with in vivo approaches. After she began her own lab we kept in touch by e-mail and at chromatin or centromere meetings, although we haven’t worked together on projects since she left. However, Yamini’s influence lingered on after she left the lab. For example, when she convinced me that we should try atomic force microscopy, which we found to be excellent advice.” Now Dalal is a senior investigator and group director in the in- tramural research program at the Center for Cancer Research at NCI/NIH in Bethesda. “We work on three major projects: understanding how the chromatin structure of centromeres contributes to its essential and conserved function; dissecting how subtle variations in mechanical properties can alter the properties of the chromatin fiber and downstream function; and figuring out why specific chromatin features are altered in cancer cells, and whether and how they contribute to disease progression,” she explains. “My lab has found it insightful to probe chromatin function using combinatorial methods, including biochemistry, genomics, molecular biology, and computational approaches.” Mary Pitman , a predoctoral fellow in her lab, shares her impressions of Dalal’s leadership style, saying, “I think as a researcher, Yamini has to be able to keep track of and lead a very multidisciplinary effort. Lab meetings in the Dalal lab span hardcore bioinformatics, cell biology, molecular dynam- ics and theory, and biochemical assays. Yamini’s strength in that setting is that she is always engaged, energetic, and is able to see the larger picture while developing a surprising

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