2022 Annual Report

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Department of Structural Biology Scientists in the Institute’s Department of Structural Biology aim to understand the most basic building blocks of biology to inform our understanding of health and disease, and to aid in the development of new, improved medications for an array of disorders. Studying the foundations of life: Our scientists are investigating the mechanisms that allow our DNA to replicate, as well as the molecules at the core of some of our most vital systems, such as temperature regulation, communication between cells, and energy production and regulation. Turning weaknesses into strengths: Our scientists are investigating molecular vulnerabilities in bacteria, such as those that cause tuberculosis and urinary tract infections, and in diseases, such as cancer, to find ways to leverage these weaknesses for treatment. Aiding drug discovery: By better understanding molecular structure and function, our scientists could aid in the development of more targeted medications with fewer side effects. 2022 HIGHLIGHTS Study reveals insights into enzyme that combats common greenhouse gas An enzyme that combats the greenhouse gas nitrous oxide (N 2 O) may one day give scientists a potent new tool for reducing the amount of the gas in the atmosphere thanks in part to findings published in Nature. The study details how the enzyme — N 2 O reductase — is assembled and offers key insights into its ability to render nitrous oxide into harmless nitrogen and water. The research was co-led by VAI's Dr. Juan Du and Dr. Wei Lü, and University of Freiburg's Dr. Oliver Einsle. 1 Molecular ‘blueprint’ illuminates how plants perceive light Plants rely on their ability to sense light for survival. But unlike animals, plants don’t have eyes full of photoreceptors to capture and convey messages from visual stimuli. Instead, plants are coated with a network of light-sensing photoreceptors that detect different wavelengths of light, allowing them to regulate their lifecycles and adjust to environmental conditions. Now, VAI and Washington University scientists have determined the molecular structure of one of these vital photoreceptors — a protein known as PhyB — revealing a wholly different structure than previously known. The findings, published in Nature by VAI’s Dr. Huilin Li and Washington University’s Dr. Rick Vierstra, may have implications for agricultural and “green” bioengineering practices. 2 VAI marks five years of discovery with cryo-EM To understand life’s building blocks — the molecules that give structure to our cells, fuel our bodies and play integral roles in health and disease — we need powerful technology that allows us to see them in deep detail. That’s where cryo-EM comes in. Short for cryo-electron microscopy, cryo-EM is a special type of technique and equipment that helps scientists zoom in on molecules in their natural state. The insights gleaned from these images tell us how molecules work, how they interact with other molecules and how they might be leveraged to design new treatments for disease. Five years ago, VAI established the David Van Andel Advanced Cryo-Electron Microscopy Suite. It includes three stateof-the-art microscopes, two of which are cryo-EM. Since then, our scientists have made many important discoveries that are reshaping our understanding of health and disease, such as new insights into how our DNA repairs itself, how our cells communicate and sense their environment, and how potential targets for new medications work. 12
Cryo-EM reveals how ‘911’ molecule helps fix DNA When something goes wrong during DNA replication, cells call their own version of 911 to pause the process and fix the problem — a failsafe that is critical to maintaining health and staving off disease. We now know more about this crucial system thanks to Dr. Huilin Li and The Rockefeller University’s Dr. Michael E O’Donnell, who revealed how a key piece of this repair process — appropriately called the 911 DNA checkpoint clamp — is recruited to the site of DNA damage. The findings, published in Nature Structural and Molecular Biology, illuminate new insights into the way cells ensure genetic instructions are properly passed from one generation of cells to the next. 3 Dr. Zheng Ruan earns prestigious K99 grant, first in VAI history Earning one’s first federal grant is a major milestone in a scientist’s career. Not only do these grants provide vital funding, but they also demonstrate the promise and innovation of research projects. Among the most prestigious of these early grants is a K99/R00 from the National Institutes of Health, which provides support throughout the transition to a scientist’s first independent research position. In summer 2022, Dr. Zheng Ruan, a postdoctoral fellow in the labs of Dr. Juan Du and Dr. Wei Lü, earned the first K99/R00 award in VAI’s 26-year history. Dr. Ruan is a structural biologist, a scientist who uses cutting-edge technology to visualize the tiny molecules responsible for our health and, when things go wrong, for disease. 4 Funding Acknowledgments Research reported in this publication was supported by: 1 European Research Council under award no. 310656 (Einsle); Deutsche Forschungsgemeinschaft under award no. CRC1381 (project ID: 403222702; Einsle) and award no. RTG2202 (project ID: 46710898, Einsle); the BIOSS Centre for Biological Signaling Studies at Albert-Ludwigs-Universität Freiburg (Einsle); a McKnight Scholar Award (Du); a Klingenstein-Simons Fellowship Award in Neuroscience (Du); a Sloan Research Fellowship in Neuroscience (Du); a Pew Scholars in Biomedical Research Award from the Pew Charitable Trusts (Du); and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award no. R01NS111031 (Du). 2 Van Andel Institute (Li), Washington University (Vierstra) and the National Institute of General Medical Sciences of the National Institutes of Health under award nos. R01GM127892 (Vierstra) and R35GM131754 (Li). 3 Van Andel Institute (Li), The Rockefeller University (O’Donnell) and the National Institute of General Medical Sciences of the National Institutes of Health under award nos. R01GM115809 (O’Donnell) and R35GM131754 (Li); the Breast Cancer Research Foundation under award no. 20-068 (O’Donnell); and Howard Hughes Medical Institute (O’Donnell). 4 Dr. Ruan is supported in part by the National Institute of Neurological Disorders and Stroke under award no. K99NS128258. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other granting organizations. Funding VAI scientists have 133 active awards totaling $166.1 million. Figures current as of November 2022 In 2022, VAI scientists earned 35 new awards totaling $41.8 million. Figures current as of November 2022 Publications In 2022, VAI scientists published 120 papers. Of these, 48 were in high-impact journals. Figures current as of November 2022 Faculty and Cores 34 Labs 9 Cores Nature Index The Nature Index, which measures institutional scientific output, ranks VAI no. 31 in the Life Science category out of the top 100 nongovernmental/nonprofits. VAI ranks no. 41 overall. RESEARCH 13 13
Page 1 and 2: 2022 Annual Report
Page 3 and 4: Table of Contents 2 A letter from D
Page 5 and 6: “From all of us at Van Andel Inst
Page 8 and 9: Department of Neurodegenerative Sci
Page 10 and 11: Department of Epigenetics Scientist
Page 12 and 13: Department of Cell Biology Our heal
Page 16 and 17: Department of Metabolism & Nutritio
Page 18 and 19: Translating impact from lab to clin
Page 20 and 21: Core Technologies & Services Van An
Page 22 and 23: Van Andel Institute Principal Inves
Page 30 and 31: A modern approach to graduate educa
Page 32 and 33: A modern approach to graduate educa
Page 34: Van Andel Institute for Education W
Page 37 and 38: K-12 EDUCATION 35
Page 39 and 40: K-12 EDUCATION 37
Page 42 and 43: Carol Van Andel Angel of Excellence
Page 44 and 45: Design & Discovery Merging the insp
Page 46 and 47: Around the World Hosted by VAI’s
Page 48 and 49: Couture for a Cure Michigan’s pre
Page 50 and 51: Hope on the Hill & The Chocolate Fa
Page 52 and 53: Signature special event sponsors We
Page 54 and 55: A decade of support: Inside Jeffery
Page 56 and 57: Positivity & perseverance: Richard
Page 58 and 59: From Purple Community to JBoard Amb
Page 60 and 61: Running for family & research Nearl
Page 62 and 63: Philanthropy Circle of Hope Anonymo
Page 64 and 65:
Van Andel Institute Board Members V
Page 66 and 67:
Van Andel Institute Board of Govern
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333 Bostwick Ave. NE, Grand Rapids,
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2022 Annual Report

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