Biophysical Society Bulletin | November 2018

Biophysicist in Profile

Biophysicist in Profile

Officers President Angela Gronenborn President-Elect David Piston Past-President Lukas Tamm Secretary Frances Separovic Treasurer Kalina Hristova Council

Heather Pinkett Areas of Research How organisms transport compounds across membranes

Lynmarie Thompson , University of Massachu- setts Amherst, worked with Pinkett in 2005 when she was on a sabbatical in Rees’s lab at Caltech. “I worked closely with Heather during my sabbatical; she taught me how to do crystallization trials on membrane proteins. I thoroughly enjoyed working with her be- cause of her infectious enthusiasm for science and her positive attitude. She also has great insights. In the Rees lab, I jokingly referred to her approach to membrane protein purifica- tion as ‘the Heather prep,’” she says. “She had recently come to the lab from a background in soluble proteins, and had immediate success in purifying and crystallizing an ABC transporter. Heather realized that for membrane proteins it is important to limit the length and number of purifica- tion steps to avoid stripping key lipids away from the protein.” Pinkett’s first presentation at a Biophys- ical Society Annual Meeting was in 2007 during her postdoc. “This exposure led to invitations to present at a Gordon Con- ference and to give talks at other insti- tutions during the first year in my faculty position,” she says. “These meetings have always provided a place for me to connect with the transport community. The talks are always amazing and often times the speakers at the meeting become my short list of who to invite for talks in my department seminar series, especially junior faculty. It is also a good place to spot potential faculty candidates. I treat the meetings like a retreat. I always come away invigorated and ready to tackle the next big problem.” After Caltech, she took a position as an asso- ciate professor in the Department of Molec- ular Biosciences at Northwestern University. “We are currently looking at how bacterial pathogens and fungals utilize the transport mechanism to survive within the host with a focus on resistance mechanisms. We study exporters (pump substrates out) and import- ers, as well as the transcriptional regulators that control expression of these transporters,” she explains. “While some ABC transporters only transport on substrate, others are quite promiscuous. Understanding how a particular transporter selects and transports a toxin, which in turn is targeted for degradation, is critical for the development of therapeutics.”

“There are so many interesting transporters that we as a field have yet to explore, and we are realizing that the diversity in ABC trans- porters is broader than we first thought,” she says. “While all use ATP binding and hydrolysis in the transport mechanism, we now see that there are mechanistic differences in selectiv- ity and regulation and we have yet to really scratch the surface in understanding how they work in concert to maintain homeostasis and circumvent toxins. Our lab is interested in the evolution and selectivity of substrates, and regulation these systems.”

Institution Northwestern University

At-a-Glance

Zev Bryant Jane Clarke Linda Columbus Bertrand Garcia-Moreno Teresa Giraldez Ruben Gonzalez, Jr. Arthur Palmer Marina Ramirez-Alvarado Jennifer Ross David Stokes Joanna Swain Pernilla Wittung-Stafeshede Biophysical Journal Jane Dyson Editor-in-Chief Society Office Ro Kampman Executive Officer Newsletter Executive Editor Rosalba Kampman Managing Editor Beth Staehle Contributing Writers and Proofreaders Dorothy Chaconas Laura Phelan

Heather Pinkett grew up around science, with a mother who worked as a nurse, and never hesitat- ed to pursue a life in science herself. After having the opportunity to participate in research as an undergraduate, she knew it was the right fit for her. She would encourage students to consider following in her footsteps to a fulfilling career: “The area of biophysics is diverse and provides so many opportunities to explore pressing questions about single molecules, the cell, and everything in between. I recently had a student tell me, ‘biochemistry was hard enough; should I pursue bio- physics research?’ So I would say, don’t be intimidated by the word. Start early and gain as much research experience as possible.”

Heather Pinkett

Heather Pinkett , associate professor in the Department of Molecular Biosciences at Northwestern University, and her sisters were always around science as they grew up. Their mother was a registered nurse and they had medical books around the house. “My mom was the one who would catch dose miscalculations on patients’ charts, so other nurses started double-checking with her. I think those stories really emphasized paying attention to detail,” Pinkett explains. She and her sisters all attended a math and science magnet high school, Manhattan Center for Science and Math in New York. Her older sister pursued biology for her undergraduate de- gree, and Pinkett followed her into science, studying chemis- try at Connecticut College. “As an undergraduate I started doing research in the laborato- ry of Professor David K Lewis , in the area of gas phase reaction kinetics. This led to an opportunity to do summer research as part of an National Sanitation Foundation-sponsored Research Experience for Undergraduates in Chemistry,” she shares. “I enjoyed collaborating with such a talented group of students and PIs all with a common goal of answering a single question using many different approaches.” As a post-baccalaureate researcher, she was part of the Pre-Intramural Research Training Award program at the National Human Genome Research Institute (NHGRI), an institute of the National Institutes of Health. Through this program, she had the opportunity to work as part of a group investigating prostate cancer, spending full days doing exper- iments, analyzing the results with the head of the research team, and then hearing the research group present those results to the larger collaborative team. “It was an amazing opportunity for me to grow as a researcher,” she says. “When it was time for graduate school, I was ready to dive in and explore a new path, which was biophysics.”

Pinkett joined the Department of Biochemistry and Molecular Biophysics at the University of Pennsylvania School of Medi- cine, with a goal of studying structural biology. “From looking at genes and mutations, I wanted a deeper understanding of protein structure and function, especially as it relates to how mutations impact function,” she explains. “ John Carpten was a postdoc at NHGRI at the time and I remember having this conversation with him about the human genome project and what comes next.” When she was in graduate school, her department offered a seminar series called George Raiziss Biochemical Rounds, in which students read articles ahead of time, attended talks, and had an opportunity to go to dinner with the speakers afterward. “I always found the talks — especially on trans- porters and channels — extremely interesting and would make sure I signed up first to go to the dinners. When it was time for me to look for a postdoc position, I focused on labs looking at structure and function of membrane proteins,” Pinkett says. She took a postdoctoral position in the lab of Douglas Rees at the California Institute of Technology (Caltech), where she worked on the structure and function of ATP-binding cassette (ABC) transporters. “As a postdoctoral fellow, I solved the structure of an ABC transporter in an inward facing confor- mation, providing the first picture of an ABC transporter in its final conformational state,” she shares. “ABC transporters harvest the energy of ATP hydrolysis to transport a wide range of molecules across membranes. Three-dimensional images of each step in the transport process are critical to understanding the molecular mechanism, but are difficult to obtain because ABC transporters are membrane proteins and challenging targets for structure determination.”

Pinkett and her husband Adam Held celebrate daughter Piper’s third birthday.

Austin Rice , one of Pinkett’s first graduate students, worked with her for five years and co-authored four papers with her concerning the mechanism of ABC transporters. “Heather is an incredibly driven and meticulous scien- tist. She is persistently optimistic,” he says. “No matter how challenging a project looked, she could see all the great possibilities in it. And when things got tough, she was very good at finding alternative paths to answer key questions.” Pinkett finds challenges exciting, and funda- mental to the broad range of research that falls into the category of biophysics. “As a field, we are always evolving and embracing new approaches to get at the complexity of biological systems. I am always open to using physics-based methods to study biologi- cal systems,” she says. “We can look at our favorite macromolecules on the molecular level to understand mechanism, then expand our focus to study networks and interactions on the cellular level, all under the umbrella of biophysics.”

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