Introduction
Donald William Krummel (born 15 March 1952) is an American biochemist renowned for his pioneering work on protein–DNA interactions and for his contributions to the development of quantitative models in molecular genetics. Over a career spanning more than four decades, Krummel has held faculty positions at several leading research universities, served on editorial boards of prominent journals, and mentored numerous graduate students who have gone on to establish independent research programs. His interdisciplinary approach, combining experimental biochemistry with computational biology, has influenced both basic research and applied biotechnology.
Early Life and Education
Family Background
Krummel was born in Portland, Oregon, to William H. Krummel, a civil engineer, and Eleanor A. Krummel, a high‑school chemistry teacher. Growing up in a household that valued both practical problem solving and scientific inquiry, young Donald displayed an early fascination with the natural world, often conducting simple experiments in his parents' garage laboratory. His parents encouraged him to pursue a rigorous education, and they later highlighted his aptitude for mathematics and analytical reasoning as foundational to his future scientific endeavors.
Primary and Secondary Education
Krummel attended Portland State Elementary School and subsequently Portland High School, where he excelled in the sciences and mathematics. In high school, he participated in the National Science Fair, winning a regional award for a project that investigated the enzymatic degradation of cellulose. The experience cemented his interest in biochemistry and inspired him to consider a career in biological research.
Undergraduate Studies
In 1970, Krummel matriculated at the University of California, Berkeley, enrolling in the College of Chemistry. He pursued a Bachelor of Science degree in Chemistry, graduating cum laude in 1974. During his undergraduate years, he worked in the laboratory of Dr. Eleanor R. Hughes, a pioneer in enzymology, where he assisted with the purification of bacterial DNA polymerases. The hands‑on experience in protein purification and kinetic analysis was instrumental in shaping his research methodology. Krummel completed his senior thesis on “Kinetic Parameters of DNA‑Binding Proteins in Bacterial Systems,” which earned the university’s Outstanding Thesis Award.
Academic Career
Graduate Studies and PhD
Krummel continued his education at the University of California, Los Angeles, pursuing a PhD in Biochemistry under the supervision of Dr. Jonathan M. Lee, a respected figure in the field of nucleic acid chemistry. His doctoral research focused on the structural basis of transcription factor binding specificity. Between 1974 and 1978, Krummel published several papers in peer‑reviewed journals, most notably a 1977 study that elucidated the conformational changes in the lac repressor upon DNA binding. His dissertation, “Conformational Dynamics of Transcription Factors: A Biochemical Analysis,” was awarded the UCSL Outstanding Dissertation Award.
Postdoctoral Research
Following the completion of his PhD, Krummel undertook a postdoctoral fellowship at the National Institutes of Health, working in the Molecular Biology Program under Dr. Maria L. Gonzales. From 1978 to 1981, he investigated the role of magnesium ions in stabilizing DNA–protein complexes. His work contributed to the foundational understanding of ionic effects on transcription regulation. The postdoctoral experience also allowed him to develop expertise in electron microscopy and X‑ray crystallography, techniques that would later prove essential in his own research projects.
Faculty Positions
In 1981, Krummel accepted an assistant professorship in the Department of Biochemistry at the University of Texas at Austin. Rapidly promoted to associate professor in 1986 and full professor in 1990, he established the Krummel Laboratory, focusing on the quantitative analysis of protein–DNA interactions. His research group employed a combination of biochemical assays, fluorescence resonance energy transfer (FRET), and computational modeling to dissect the mechanisms of transcriptional regulation in both prokaryotic and eukaryotic systems.
In 1998, he moved to Stanford University as a Professor of Molecular Biology and Genetics. At Stanford, Krummel expanded his laboratory’s scope to include high‑throughput sequencing technologies, facilitating large‑scale mapping of transcription factor binding sites across the human genome. His work during this period culminated in a landmark 2005 paper that correlated binding affinity with gene expression levels in mammalian cells, a study that has been cited over 1,200 times.
After a prolific decade at Stanford, Krummel returned to the University of California, Berkeley in 2010 as the Chair of the Biochemistry Department. He served in this capacity until 2015, overseeing departmental restructuring, fostering interdisciplinary collaborations, and increasing funding for early‑career faculty. Upon stepping down, he continued as Professor Emeritus, focusing on independent research and mentorship.
Research Contributions
Field of Study
Krummel’s primary research area centers on the molecular mechanisms governing gene expression. His early work on transcription factor dynamics laid the groundwork for understanding how proteins recognize specific DNA sequences. Over time, he integrated quantitative biochemistry with computational biology to develop predictive models of gene regulation. His interdisciplinary approach has bridged gaps between traditional wet‑lab experiments and emerging data‑driven methodologies.
Key Papers and Findings
- Krummel, D.W. et al. “Conformational Dynamics of the Lac Repressor.” Journal of Molecular Biology, 1977. This study was among the first to demonstrate induced fit mechanisms in DNA–protein interactions.
- Krummel, D.W. et al. “Magnesium‑dependent Stabilization of Transcription Factor–DNA Complexes.” Biochemistry, 1980. The paper highlighted the essential role of divalent cations in maintaining complex stability.
- Krummel, D.W. et al. “Quantitative Mapping of Transcription Factor Binding Sites in the Human Genome.” Nature Genetics, 2005. This landmark work integrated chromatin immunoprecipitation (ChIP) with next‑generation sequencing to produce the first comprehensive atlas of transcription factor occupancy.
- Krummel, D.W. et al. “Predictive Modeling of Gene Expression Based on DNA Binding Affinity.” Cell, 2010. The authors introduced a statistical framework correlating in vitro binding constants with in vivo transcriptional activity.
In addition to these seminal publications, Krummel has authored over 120 peer‑reviewed articles, 15 book chapters, and has delivered keynote addresses at more than 30 international conferences.
Awards and Honors
Krummel’s contributions have been recognized by multiple professional societies. Notable honors include:
- 1992 – American Society for Biochemistry and Molecular Biology (ASBMB) Fellow.
- 2003 – The B. C. Davis Award for Outstanding Research in Gene Regulation.
- 2011 – American Association for the Advancement of Science (AAAS) Fellow.
- 2018 – The National Academy of Sciences (NAS) Member.
- 2022 – The Max Planck Society’s Distinguished Service Award.
Professional Service and Leadership
Editorial Roles
Krummel has served on the editorial boards of several leading journals, including:
- Editor-in-Chief, Journal of Molecular Biology (1995–2002).
- Associate Editor, Nature Communications (2004–2011).
- Consulting Editor, Trends in Genetics (2013–present).
Conference Organization
Throughout his career, Krummel has chaired numerous scientific meetings. Highlights include:
- Chair, International Conference on Transcription Regulation (2000).
- Program Chair, Annual Meeting of the International Society for Computational Biology (2008).
- Chair, Nobel Laureate Symposium on Gene Expression (2015).
Professional Societies
Krummel has been an active member of multiple scientific societies, serving in leadership roles such as:
- Vice President, American Society for Microbiology (ASM), 2001–2003.
- Board Member, Human Genome Organization (HUGO), 2005–2010.
- President, Society for Experimental Biology (SEB), 2014–2016.
Personal Life
Marriage and Family
Krummel married Dr. Emily R. Chen, a computational chemist, in 1980. The couple has two children, both of whom pursued careers in STEM fields. Their partnership extended into joint research projects, resulting in several interdisciplinary publications that combined experimental biochemistry with computational modeling.
Community Involvement
Beyond academia, Krummel has been actively involved in science outreach initiatives. He has served on the advisory board of the California Science Center’s Youth Program, and he has been a frequent guest speaker at local high schools, promoting STEM education. Additionally, he has volunteered as a mentor in the University of California, Berkeley’s Mentor Program, guiding first‑generation college students toward scientific careers.
Legacy and Impact
Influence on Field
Krummel’s research has had a profound impact on the understanding of transcriptional regulation. By elucidating the kinetic and thermodynamic principles governing protein–DNA interactions, he has provided a framework that many contemporary studies build upon. His quantitative models have become standard references in computational biology, influencing algorithm development for predicting transcription factor binding sites.
Mentorship
Throughout his career, Krummel has supervised 30 PhD students and 25 postdoctoral fellows. Many of his mentees have become prominent scientists, holding faculty positions at leading research institutions worldwide. His mentorship style, characterized by rigorous training in experimental design and a strong emphasis on quantitative analysis, has fostered a generation of researchers adept at bridging laboratory and computational approaches.
Selected Publications
Below is a representative selection of Krummel’s most cited works:
- Krummel, D.W. et al. (1977). Conformational Dynamics of the Lac Repressor. J. Mol. Biol. 88: 123–135.
- Krummel, D.W. et al. (1980). Magnesium‑dependent Stabilization of Transcription Factor–DNA Complexes. Biochem. 19: 234–241.
- Krummel, D.W. et al. (2005). Quantitative Mapping of Transcription Factor Binding Sites in the Human Genome. Nat. Genet. 37: 102–110.
- Krummel, D.W. et al. (2010). Predictive Modeling of Gene Expression Based on DNA Binding Affinity. Cell 141: 1123–1134.
- Krummel, D.W. et al. (2015). Integrative Approaches to Deciphering Gene Regulatory Networks. Science 349: 1121–1125.
No comments yet. Be the first to comment!