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Biophysicist in Profile

Arne Gennerich

Arne Gennerich

July/August 2023 // 2450

Arne Gennerich grew up in the small village of Bremke in Ger­many. “There my afternoons were spent exploring the local forest or engaging in hands-on activities like repairing bicy­cles, radios, and TVs,” he shares. “One of the highlights was our village’s quarterly pickup times for bulky waste, where residents placed items outside their houses to be collected the following day. My friends and I eagerly scoured through the discarded treasures, often finding dysfunctional bicycles and TVs that I could repair. These experiences not only honed my practical skills but also fostered a problem-solving mind­set. Through dismantling and fixing these objects, I developed the ability to troubleshoot and mend electronic devices. This early exposure to problem solving laid a foundation for my future endeavors.”

Driven by his fascination with electronic circuits, he made the decision at age 16 to leave school and pursue vocational training in electronics. “I was fortunate to secure a position at the renowned Max-Planck Institute for Biophysical Chemistry in Göttingen, Germany, where Nobel Laureate Stefan Hell con­ducts his groundbreaking work. Over the course of four years, I engaged in practical work at the institute’s electronics work­shop while simultaneously receiving theoretical training at the local technical vocational school,” Gennerich explains. “While I thoroughly enjoyed the vocational training and the valuable knowledge I gained, I felt a desire to achieve more in my life. This realization prompted me to return to school for one year to obtain a technical college entrance certificate, which would enable me to pursue higher education. Subsequently, I en­rolled in the telecommunications engineering program at the University of Applied Sciences in Wolfenbüttel, Germany—a specialized technical university offering Bachelor of Science degrees tailored to industry roles.”

During that time, he reconnected with a familiar face from his hometown, Heiner Wedemeyer. Wedemeyer was pursuing an MD-PhD degree and suggested that Gennerich work on his diploma thesis in the lab of Detlev Schild at the Medical School of the University of Göttingen. He connected with Schild quickly, and the two planned a project that would leverage his skills in electrical and software engineering. “While I was working on my thesis, Detlev introduced the idea of studying physics to me. He emphasized that while one can acquire knowledge of biology from textbooks, studying physics at a university provides the foundation to derive complex equa­tions and truly comprehend how the world functions. Inspired by his perspective, I made the decision to enroll at the Uni­versity of Göttingen to pursue an MS degree in physics. At the age of 25, I embarked on this new academic journey, starting from the first semester and surrounded by students who were five years younger than me,” he says.

Following the completion of his master’s degree, Gennerich continued his academic journey, pursuing a PhD in physics in Schild’s lab. “I transformed the fluorescence correlation spec­troscope (FCS) I built for my master’s degree into a confocal laser-scanning microscope combined with FCS capabilities. This advanced microscope allowed me to capture images of cultured neurons and conduct FCS measurements in different regions of a neuron. This phase of my scientific work signifi­cantly enhanced my skills in optical engineering and software programming. I utilized C++ programming under real-time Li­nux to control galvanometer scanners, access photon-count­ing hardware (which I also constructed), and perform calcu­lations and visualization of acquired fluorescence images in real time,” he recalls. “During this period, my research took a particular focus on the microtubule-based motor proteins, kinesin and cytoplasmic dynein. Using the microscope I built, I observed the fascinating directional transport of auto-flu­orescent mitochondria within neurons’ axons and dendrites, which sparked my interest in cytoskeletal motor proteins. I delved into the pioneering research of scientists like Joe Howard, Steve Block, Ron Vale, Nabutaka Hirokawa, and others. Their groundbreaking papers shed light on the kinesin walking mechanism through compelling single-molecule studies, uti­lizing advanced home-built microscopes such as optical twee­zers and total internal reflection fluorescence microscopes.”

He developed an interest in single-molecule biophysics and, eager to explore the area further, decided to pursue a post­doctoral position in the United States. From November 2003 to October 2008, he worked as a postdoctoral fellow in Vale’s lab at the University of California, San Francisco. “My primary focus in Ron’s lab was on yeast cytoplasmic dynein,” Genner­ich shares. “I conducted force measurements on dynein using optical tweezers and also maintained and improved the lab’s optical tweezers setup. Additionally, during my time in the lab, I gained expertise in performing mutagenesis studies and ac­quired knowledge in expressing and purifying motor proteins.”

In 2008, when he began seeking group leader and assistant professor positions and applied for positions in Germany, he encountered an unexpected obstacle. “To my surprise, during interactions with search committees, directly or indirectly, I was informed that I was considered too old. At the time, I was 37 years old (as a result of my unconventional education), and I was told that there was an age limit of 35 for group leader positions,” he says. “The age discrimination I experienced in Germany was disheartening, especially considering that I had spent over seven years in the United States, where job ap­plications do not include birth information or profile pictures for obvious reasons. This experience left me astonished and disappointed. Ultimately, I found solace in remaining in the United States, a country that I deeply love.”

Gennerich is now a professor of biochemistry at the Albert Einstein College of Medicine in the Bronx, New York. “My research focuses on elucidating the molecular functions of kinesin motors and the cytoplasmic dynein-dynactin motor complex. To study these motors, we utilize diverse expression systems such as Escherichia coli, budding yeast, insect cells, and mammalian cells for structure-function investigations,” he details. “Currently, one of our research goals is to unravel the mechanism underlying the remarkable superprocessiv­ity of the kinesin-3 motor, KIF1A, which is predominantly expressed in neurons. Superprocessivity refers to its excep­tional ability to traverse micrometer distances along microtu­bules without detaching. Mutations in the KIF1A gene lead to severe neurodevelopmental and neurodegenerative disorders known as KIF1A-associated neurological disorders (KAND). In our research, we collaborate closely with Wendy Chung from Columbia Medical School and the patient advocacy group KIF1A.org. Wendy, a clinician scientist who treats KAND pa­tients, and KIF1A.org share our commitment to enhancing the quality of life for individuals affected by KAND and expediting the development of potential treatments.”

He continues, “Understanding the molecular basis of KAND is a challenging endeavor, primarily due to the limited knowl­edge about the underlying molecular mechanism of KIF1A. To address this gap, my collaborator Hernando Sosa, a cryo-EM specialist at Einstein, and I recently secured funding from the Deerfield Managing Company to establish a startup company. The primary aim of this venture is to leverage structure-guid­ed drug design approaches to facilitate the discovery of po­tential therapeutic interventions for KAND and other human diseases caused by mutations in microtubule-associated motors.”

In addition to his research and supporting the career success of graduate students and postdocs at Einstein, Gennerich has organized various career development events. He initiated, designed, and has presented the annual postdoc seminars “Academic Job Hunt: Tips & Tricks for Successful Interviewing for an Assistant Professor Position” and “How to Prepare for and Choose the Best Postdoc for You, including the Potential Benefits of a Second Postdoc” since 2015. Recognizing that not all graduate students would pursue academic careers, Gennerich also created and taught the graduate seminar “Ap­plying for Jobs outside Academia: Essential Steps during Your PhD to Succeed in the Job Market” since 2014. The feedback received for these seminars was extremely positive, with numerous postdocs seeking his guidance in their job search­es. He takes great satisfaction in witnessing young scientists successfully establish their own labs, as evidenced by the continued contact with many postdocs whom he assisted in their job applications and interview processes.

Outside of his work, Gennerich leads an active life in New York City. “I cherish the time I spend with my girlfriend, who is not a scientist, and her seven-year-old daughter. Together, we engage in activities that bring us joy and strengthen our bond. We enjoy engaging in discussions about politics and current events during our dinners, which often leads us to discover new books, movies, or ways to enhance our lives. I consider myself fortunate to share several hobbies with my girlfriend, including walking and running together, indoor climbing, and learning tennis. We also enjoy traveling together, exploring the world, and creating new experiences” he reveals. “Addi­tionally, I love riding motor bikes (I own a BMW R18 cruiser) and have a deep appreciation for hazy IPAs and the company of friends who share my love for this type of beer.”