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Biophysicist in Profile

Daryl Eggers

Daryl Eggers

September 2021 // 3248

Like many biophysicists, Daryl Eggers, Professor of Chemistry at San José State University (SJSU), excelled in math and science courses in high school. “Everyone said I should become an engineer, so I enrolled as a chemical engineering major at Rose-Hulman Institute of Technology (RHIT) in 1977 without a true understanding of what my job options would be after graduation,” he explains. RHIT was just an hour’s drive west of his home town of Plainfield, Indiana, “making it easy for me to visit family on weekends during my undergraduate education. I realize now how incredibly fortunate I was to be able to focus on my studies without working in a part-time job at the same time, a luxury that most of my current students do not enjoy.”

Biology courses were not offered at RHIT at the time, but he took an elective course in biochemical engineering “where I was introduced to the four classes of biomolecules in the first chapter of a classic textbook by Bailey & Ollis,” he says. “That material excited me and remained in the back of my mind as I pursued my first job.”

Following his graduation from RHIT in 1981, he accepted a job offer with M.W. Kellogg, an engineering and construction company in Houston, Texas. “Naively, I thought I would work for Kellogg the rest of my career, but I quickly learned that there was no job security in a company where the contracts and workload parallel the ups and downs of the oil industry. After losing many lunch date friends to layoffs, I started thinking seriously about returning to school and decided to apply to master’s degree programs that offer a concentration in biochemical engineering; my new goal was to land a job in the booming biotechnology industry,” Eggers shares.

At that point he did not plan on pursuing a PhD, as he did not view himself as qualified or worthy of the degree and did not have a clear picture of what life in graduate school would be like. “I ended up at University of California, Berkeley and was accepted into the bioengineering group of Harvey Blanch where I was surrounded by some amazing people and where I gained my first research experience,” he says. “Although several labmates suggested that I stay on and get my PhD, I followed my plans to leverage the MS degree into a job in biotechnology.”

He joined the research wing of Syntex, a pharmaceutical company based in Palo Alto, California and found it to be an ideal job for a bioengineer: working with a small team in charge of expressing, purifying, and increasing production of recombinant proteins from bench scale to pilot plant. “This experience improved my confidence as a scientist, but I realized that I could not advance far up the research ladder without a PhD. One of my projects during this period involved the refolding of a protein that I had purified from inclusion bodies. A frustratingly low refolding yield led me to the library, but I found the literature on protein folding in the 1980s to be very unsatisfying. ‘Maybe I could go back to school (again), pursue some of my own ideas on protein folding for a thesis, and then rejoin industry research as a project leader?’” he thought. “At the time, I wasn’t entangled with house payments or any financial obligations, so I decided to apply to some top PhD programs in California. I decided to target pharmacology programs, and I was delighted and honored to be admitted to the Pharmacology Department of the School of Medicine at University of California San Francisco (UCSF).”

He persevered through ups and downs at UCSF and completed his PhD degree in 1997. “My thesis research was performed in the laboratory of William J. Welch, one of the first scientists to characterize the heat shock response and to identify specific proteins that act as molecular chaperones. Thus, my attention was turned more toward protein folding in the cell, versus the refolding of recombinant proteins in vitro,” he explains. “During this time, I had a fateful discussion in the office of Ken Dill, then at UCSF, where I expressed my concern that the scientific community was overstating the importance of chaperones and where I put forward the idea that the crowded environment of the cell had something to do with the high fidelity of protein folding in vivo; I had recently read some papers by Allen Minton that I thought might have relevance to protein folding, even though the early Minton papers did not mention proteins. Ken showed me the cover of a Science issue that featured some colorful proteins encapsulated in silica glass. It didn’t hit me immediately, but this paper, from a group at University of California, Los Angeles (UCLA), led to the single most important move of my career.”

Eggers had always planned to return to industry right after graduate school, but after applying to some local biotechnology companies and receiving no response, he started to think about an academic postdoctoral position. “I went back to the paper recommended by Ken Dill and realized that the glass encapsulation technique might serve as a model for molecular crowding and confinement effects. I contacted Joan S. Valentine, one of the co-authors, and she responded to suggest we meet in San Francisco while she was there for a meeting of journal editors. I can still remember our first encounter outside of the Moscone Center. I think we both sensed this was a scientific match made in heaven, and I soon received an invitation to join her group at UCLA,” he shares. “Working in the Valentine laboratory was one of the most enjoyable experiences of my life. Valentine group meetings were boisterous affairs filled with free-flowing ideas and energy, and our mentor understood the importance of a work-life balance. I rarely visited the lab on weekends and found time to serve as an LGBT mentor through a pioneering program run by Pat Alford-Keating of the UCLA Psychology Department. On the scientific front, my first experiments with glass-encapsulated proteins were analyzed on an old circular dichroism instrument in Jim Bowie’s lab, ultimately leading to the two most-cited publications of my career. During this time, I was given a chance to teach metabolism to biochemistry majors during summer session. I was confident that I could handle the teaching assignment, but I did not anticipate that I would like teaching so much. This enlightenment caused me to reconsider my future. Maybe I should pursue a tenure-track faculty position where I am valued as both a creative researcher and effective teacher?”

 He did just that, obtaining a position in 2002 with the Chemistry Department at SJSU. “My initial projects at SJSU were an extension of my glass encapsulation studies at UCLA. However, an early puzzling observation related to apomyoglobin structure in the glass caused my interest and attention to shift from crowding effects to hydration effects. Today my lab’s main focus is water and how water influences binding and conformational equilibria. Using multiple biophysical techniques, my lab aims to demonstrate that the classical equations of thermodynamics for binding equilibria have obscured our understanding of solvation effects; my group has published an alternative equation for equilibria that includes an explicit accounting term for water and that reveals the binding constant, K, is actually a variable that changes with product concentration when solvation is a significant contributor to the overall thermodynamics. Toward this goal, two papers have been published and two more papers are in the making, all featuring results that suggest our approach is a step in the right direction. In addition, I am currently involved in a collaboration that examines the binding of potential therapeutic molecules to virus proteins. My lab is using microscale thermophoresis to measure the interaction of glycodendrimers, made by Katherine McReynolds at CSU Sacramento, with the surface proteins of HIV and SARS-CoV-2.”

Eggers shares, “In the beginning, I thought my research was the most important, career-defining aspect of my job. Now, as I near retirement from academia, I realize my true legacy lies with the former students at SJSU who passed through my lab or classroom.”

Outside of work, Eggers and his husband David follow the San Francisco Giants baseball team and enjoy traveling to figure skating competitions and watching the television game show Jeopardy!. And he says, “We spend a lot of our time spoiling our kid, a yellow Labrador Retriever named Dempsey.”



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