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Biophysicist in Profile

Sharyn Endow

Sharyn Endow

June 2023 // 2221

Sharyn A. Endow, Full Professor of Cell Biology at Duke University, grew up in rural Oregon. “The nearest town was three miles from my home and had a population at the time of only around 300 people. My parents owned an orchard and raised apples, pears, and cherries. My parents’ land was near Mt. Hood and on a hill that overlooked the Hood River Valley—the views were spectacular,” she shares. “As a child, my siblings and I went on long walks along the irrigation waterways on my par­ents’ property and played in the wooded areas, picking wild berries and hazelnuts. It was an idyllic childhood and far removed from the real world—in retrospect, it is amazing that I ended up doing scientific research in biophysics.”

In high school, Endow had a wonderful teacher who inspired her love of science. “Mr. Bill Griffith taught almost all my high school science courses. He taught Chemistry, Phys­ics, and Science Seminar, in which a small group of students, including myself, learned semi-quantitative microanalysis as seniors in high school. We also did independent projects in Science Seminar. My projects included growing crystals from the chemicals in the supply room and culturing chick embry­os in the laboratory,” she explains. “I submitted a project for the Westinghouse Science Talent Search and I was thrilled to be among the national semi-finalists and one of the Oregon state awardees my senior year.”

Endow graduated as valedictorian from Wy’East High School in Hood River Valley, and then attended Stanford Universi­ty for her undergraduate studies, majoring in biology. “The courses at Stanford were exceptionally well taught. I espe­cially remember the course in evolutionary biology which was taught by Peter Raven and Paul Ehrlich, and a few other pro­fessors, and the co-evolution of plants and pollinators, as well as the impact of population growth on the world,” she says. “As a senior, I took the biochemistry course that was given by the Biochemistry Department for the medical students. The faculty included Paul Berg, Arthur Kornberg, Dave Hogness, and other notable faculty from the Biochemistry Department in the Stanford University Medical School. The lectures were stories of discovery and insight into the impact of biochemis­try in understanding the basis of human diseases. I still have my lecture notes from the course.”

After completing her bachelor’s degree, she attended Yale University for graduate studies, earning a Master of Philoso­phy and then a PhD in Molecular and Cell Biology. She recalls, “I was a thesis student of Joe Gall, who is a cell biologist and worked on problems that many of us as students thought were taken directly from E. B. Wilson’s The Cell. Joe applied mo­lecular biology methods to classical problems in cell biology and discovered ribosomal gene amplification in oocytes of amphibia and other organisms, as well as the molecular basis of other classical cell biological observations.”

Upon leaving Yale, Endow undertook a position as a postdoc­toral fellow at Cold Spring Harbor Laboratory (CSHL) in the lab of Rich Roberts, where she learned molecular biology for just over a year. Her second postdoc was at the now-defunct MRC Mammalian Genome Unit in Edinburgh, Scotland under Peter M. B. Walker, where she worked in the laboratory of Ed Southern for two and a half years. “These were both forma­tive experiences and extremely exciting for different reasons. CSHL was exciting because of both the cutting-edge science and the famous (and infamous) scientists who came to the Laboratory to attend the summer and fall CSHL meetings. A few of the scientists from the former Carnegie Institution of Genetics were still there, including Barbara McClintock and Alfred Hershey, both of whom I was awed to see, not to men­tion to meet,” she says. “The MRC Genome Unit was exciting, again because of the science, and also because living in the UK and doing science there was so different from the USA. While I was in Edinburgh, I started working on the ribosomal genes (rDNA) of Drosophila and changes in rDNA copy num­ber in polytene cells and during magnification, a genetically induced increase in rDNA gene number.”

Endow’s next move was to begin a faculty position at Duke University, where she continued work on the mechanism of rDNA copy number regulation and then entered the field of motor proteins through molecular work in cloning a gene in Drosophila that affects rDNA number when mutated. “This gene turned out to encode kinesin-14 Ncd, which is an un­usual kinesin microtubule motor protein in that it moves on microtubules in the opposite direction as kinesin-1, the first discovered member of the kinesin family. Cloning the gene took around five years, because this was before the genome sequencing projects. We first made a transposable ele­ment-induced ncd mutant and then cloned the gene locus by chromosome walking from a previously cloned DNA fragment.

After cloning and sequencing the ncd gene, I collaborated with a colleague, Steve Henikoff, to discover the identity of the protein. Steve, at the time, had been obtaining new DNA database releases as they came out to search for homolo­gous DNA sequences, as this was not only before the genome sequencing projects, but also before the establishment and widespread accessibility of the current DNA databases. Steve found the homology of the Ncd protein to the microtubule motor protein kinesin-1, which had just been deposited into the DNA database. This was exciting because we knew that Ncd had a role in division and mitosis workers at the time were searching for the anaphase A motor—Ncd did not turn out to be the long-sought anaphase A motor (we and others are still looking!!), but the findings that we made with collab­orators since discovering that Ncd is a kinesin motor protein have been highly informative about the role of motor proteins in division,” Endow explains.

“One collaborator, Ted Salmon at nearby [University of North Carolina], Chapel Hill, was highly important in establishing that Ncd was a microtubule motor protein that moved to microtubule minus ends, in contrast to kinesin-1, which is a plus-end-directed microtubule motor protein. These find­ings were reported at a Biophysical Society Annual Meeting, which led to my meeting other workers in the motors field. My laboratory then became involved in further studies using biophysical methods with collaborators that include Keiko Hirose, Hideo Higuchi, and Hee-Won Park. An especially reward­ing aspect of working in the motors field, given my Japanese ancestry, has been meeting the leading motors biophysicists from Japan.”

Endow is currently a Full Professor of Cell Biology at Duke University. “Our present work is to uncover the kinesin motor mechanism of function using mutants and structural studies. We are currently collaborating with Ryo Nitta-san and Tsuy­oshi Imasaki-san at Kobe University on structural studies of a kinesin-14 mutant by cryo-EM,” she reports. “Another project in which we are very involved is to adapt a kinesin-14 motor into a tension sensor to measure loads across the motor in the spindle—this is being done in collaboration with Dr. Brent Hoffman at Duke University.”

In addition to her research, Endow has contributed to the field through outreach, including working on many projects during her time as a member of the BPS Education Committee. “I have been very fortunate to have the Biophysical Society as a collaborator in STEM outreach that I use as ‘Broader Impacts’ for [a National Science Foundation] Grant Award. This came about through my membership on the BPS Education Com­mittee and attendance at an Annual Meeting where I noticed the small wooden microscopes that were being distributed by Echo Labs as a vendor giveaway. I took one home and thought they would be ideal for STEM outreach in light microscopy, so I emailed the company and asked if they would make a gift to the Biophysical Society of the wooden microscope kits that the Education Committee could use for outreach.” She adds, “Together with Chroma Technology Corp., Echo Labs made a gift of 500 kits to the Society in 2016 that the BPS and So­ciety members have been using for outreach in the USA and around the globe since then. The wooden microscopes can be assembled in 15–20 minutes from the kits, and young people of all ages become enthralled in building the microscopes and using them. The small microscopes have only a single lens that is not corrected for chromatic aberration, but they pro­duce amazing images using a cell phone camera to illuminate and magnify the specimens.”

Endow shares that her experience as a member of the Bio­physical Society has been special due to the connections with scientists in her field, often fostered by Subgroup member­ship, and because of the personal connections made with the Society’s small staff: “I recall arriving at a meeting in Singa­pore and being greeted by a hug from Ro Kampman, then Ex­ecutive Officer of BPS. Imagine traveling halfway around the world and being warmly greeted by the Biophysical Society Executive Officer in a foreign country! Attending the Annual Meeting and seeing the Society staff is like being welcomed as friends by the staff. I regard the Society as fortunate in having staff that help make the office run so smoothly (at least from the perspective of a BPS Member!). The Biophys­ical Society is also fortunate in having as Executive Officer Jennifer Pesanelli, who effectively guides the Society in its new ventures. An example of a new venture that has had a large positive impact is the President’s Black in Biophysics Sym­posium at the recent Annual Meeting. The newly launched Diversity, Equity, and Inclusion Resources for Society mem­bers also promises to have a large positive impact.”