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Expanding the Toolbox SPRING 2019 INVESTING IN DISCOVERY EXPANDING LSI-led projects help keep U-M on the THE TOOLBOX cutting edge of basic science research How the LSI is developing new tools to advance scientific discovery LET’S TALK SCICOMM Public engagement in the digital age CONTENTS DEPARTMENTS Expanding the Toolbox How the LSI is developing new 01 From the Director 8 tools to advance scientific 02 News & Updates discovery 26 Perspectives 30 Victors for Discovery 35 Voices of the Faculty 36 Profiles 40 Inside the LSI Investing in Discovery 46 Year in Photos LSI-led projects help keep U-M 15 on the cutting edge of basic science research ON THE COVER New tools help to expand and advance scientific discovery. Photos: Peng Li (wrench image), Erin Grimm (hammer image), Let’s Talk SCICOMM Stephanie King (saw image) Public engagement in the 21 digital age LSI Magazine is published annually by the U-M The Life Sciences Institute REGENTS OF THE The University of Michigan, as an equal Life Sciences Institute University of Michigan UNIVERSITY OF MICHIGAN opportunity/affirmative action employer, 210 Washtenaw Avenue Jordan B. Acker, Huntington Woods complies with all applicable federal and ROGER D. CONE, PH.D. Ann Arbor, MI 48109-2216 Michael J. Behm, Grand Blanc state laws regarding nondiscrimination and Director Mark J. Bernstein, Ann Arbor affirmative action. The University of Michigan (734) 763-1200 | [email protected] Paul W. Brown, Ann Arbor is committed to a policy of equal opportunity ANNA SCHORK, J.D. Shauna Ryder Diggs, Grosse Pointe for all persons and does not discriminate Managing Director Send address changes to the above address Denise Ilitch, Bingham Farms on the basis of race, color, national origin, or email. Ron Weiser, Ann Arbor age, marital status, sex, sexual orientation, EMILY KAGEY Katherine E. White, Ann Arbor gender identity, gender expression, disability, Editor & Manager of Communications and Copyright © 2019 Regents of the University Mark S. Schlissel, ex officio religion, height, weight, or veteran status Marketing of Michigan in employment, educational programs and activities, and admissions. Inquiries or IAN DEMSKY complaints may be addressed to the Senior Contributing Editor Director for Institutional Equity, and Title IX/Section 504/ADA Coordinator, Office STEPHANIE KING for Institutional Equity, 2072 Administrative Designer & Illustrator Services Building, Ann Arbor, Michigan 48109-1432, (734) 763-0235, TTY (734) LAURA J. WILLIAMS 647-1388, [email protected]. Director of Development For other University of Michigan information call (734) 764-1817. LSI MAGAZINE / SPRING 2019 FROM THE DIRECTOR Leisa Thompson Photography t is hard to overestimate the power that new tools bring David Sherman and Ashootosh Tripathi were awarded to scientists’ ability to make discoveries — and we are Biosciences funds to advance a nascent program in natural fortunate to be in a period of accelerating development products drug discovery, including a core lab for all U-M Iof new technologies in the life sciences. For example, investigators. Natural products synthesized by microbes the convergence of chemistry, physics and computational often make very good drugs (think antibiotics, anti- power have resulted in striking advances in both light and malarial treatments and many cancer drugs); however, electron microscopy, which will enable even further insight the chemistry to convert these products into promising into biological systems and processes. pharmaceuticals can be daunting. Consequently, most major pharmaceutical companies have given away, or This issue of the LSI Magazine focuses on some of the even destroyed, their natural products collections. remarkable discovery resources that LSI investigators and core laboratories bring to the entire faculty of the Sherman and his colleagues are linking semipurified University of Michigan and, indeed, the world. The cover extracts from a unique collection of approximately 5,000 article, “Expanding the Toolbox,” focuses on three LSI live microbial strains with the biosynthetic tools to identify, investigators who are developing new methodologies in overproduce and even modify active natural products. This chemistry, biophysics and computing that will undoubtedly unique set of tools for solving difficult problems in drug enable profound new discoveries across the biosciences. discovery will make the U-M a leader and best in this field. LSI projects were also selected as two of the five major There’s much more going on at the LSI than we can pack scientific research proposals funded by the presidential into a single magazine issue, so I invite you to follow U-M Biosciences Initiative in 2018. These cross-disciplinary our progress throughout the year by signing up for our projects will strengthen the university’s ability to solve quarterly e-newsletters and by joining the conversation on critical problems in the biosciences through advanced Twitter, @UMLifeSciences. microscopy and natural products drug discovery. The University of Michigan is already a national leader in Sincerely, cryo-electron microscopy (cryo-EM), and Biosciences funding will allow LSI investigators Melanie Ohi, Michael Cianfrocco and Janet Smith to peer even further into the mysteries of the cell. Conventional cryo-EM allows scientists to determine the atomic-level structure of Roger D. Cone, Ph.D. molecules purified from the cell. By creating a program Mary Sue Coleman Director, Life Sciences Institute in cryo-electron tomography, they intend to develop the methods needed to determine the 3-D structure of macromolecules inside of cells.This will be revolutionary. NEWS & UPDATES NOT SO FAST THERE S. XU LAB A research team led by the Life Sciences Institute has To better understand how the interactions between uncovered a cause of declining motor function and increasing cells changed as worms aged, Xu and his colleagues frailty in tiny, aging worms — and a way to slow it down. investigated the junctions where motor neurons communicate with muscle tissue. The findings identify a molecule that can be targeted to improve motor function, and indicate that similar They identified a molecule called SLO-1 (for “slowpoke pathways may be at play in aging mammals as well. potassium channel family member 1”) that acts as a regulator for these communications. The molecule As humans and animals age, our motor functions dampens neurons’ activity, slowing down the signals from progressively deteriorate. Millimeter-long nematodes neurons to muscle tissue and reducing motor function. exhibit aging patterns remarkably similar to those of other animals. And they only live about three weeks, making The researchers manipulated SLO-1, first using genetic them an ideal model system for studying aging. tools and then using a drug called paxilline. In both cases, they observed two major effects in the roundworms. Not “We previously observed that as worms age, they gradually only did they maintain better motor function later in life, lose physiological functions,” explains Shawn Xu, Ph.D., they also lived longer than the control worms. professor at the LSI and senior study author. “Sometime around the middle of their adulthood, their motor function begins to decline. But what causes that decline?” Heiti Paves/iStock/Thinkstock 2 LSI MAGAZINE / SPRING 2019 NEWS & UPDATES PUTTING THE BRAKES ON METABOLISM RESEARCHERS LIN LAB IDENTIFY NEW A hormone produced by the liver tells the body to downshift its metabolism POTENTIAL DRUG when it’s expending a lot of energy, LSI researchers have found. TARGET FOR HUNTINGTON’S Scientists in the lab of LSI professor Jiandie Lin, Ph.D., discovered that DISEASE WEISMAN LAB the hormone tsukushi (or TSK) was elevated in mouse tissue when mice were burning a lot of energy, such as when they needed to maintain body A multi-institutional team of temperature in cold environments. researchers, including the LSI’s Weisman lab, identified a new drug The researchers believe TSK is putting a “brake” on metabolism and target for treating Huntington’s dampening energy expenditure. disease, a fatal neurological disorder for which there currently Removing this brake had metabolic benefits for the mice. When mice were is no cure or preventative therapy. temporarily fasted, those lacking TSK lost significantly more weight than normal mice. And when fed a high-fat diet, normal mice approximately The researchers identified an doubled in weight — while the mice that lacked TSK experienced only about enzyme that, when inhibited, a 30 percent increase in weight and displayed better metabolic parameters. appears to help clear out the mutant proteins that accumulate in cells The research reveals a potential target for treating metabolic disorders. and lead to the disease. The study, which included a fruit fly model of Huntington’s disease, paves the way for mammalian studies — a precursor to eventual development and testing of a drug in humans. “What’s most exciting here is that not only can the fruit flies tolerate the lack of this enzyme,” says Lois Weisman, Ph.D., “but it’s actually making them better.” Stephanie King, LSI SCIENTISTS HAVE REVEALED THE FIRST STEPS INVOLVED IN A MICROBE’S SYNTHESIS OF A POTENT NERVE TOXIN. “THE ADVANCE COULD HELP TO MAKE THE COMPOUND, SAXITOXIN, MEDICALLY USEFUL. —Nature Research Highlights on work led by LSI faculty member Alison Narayan, Ph.D., on an enzyme involved in manufacturing saxitoxin. By modifying the toxin’s precursors, the team aims to transform the deadly poison for beneficial use. ” LSI MAGAZINE / SPRING 2019 3 NEWS & UPDATES RECEPTOR PROTEIN IN THE BRAIN CONTROLS THE BODY’S FAT ‘RHEOSTAT’ CONE LAB A team of scientists from the LSI and Vanderbilt experiences some sort of metabolic stress that shifts University has uncovered the function of a protein energy levels — eating too much or too little, for example that has been confounding researchers for more than — MC3R ensures that the balance of energy and fat in the two decades — and has introduced a new concept in body does not drift too far in either direction. metabolism research.
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