When Judith Kimball began studying animal development in nematodes. Caenorhabditis EleganceShe wasn’t thinking about a career in science. “I just wanted to tackle a problem that was fundamental but still a mystery – a black box,” she says. “I was fortunate that this approach led to a career.” His “black box” focus led Kimble to important discoveries, many of which came with “eureka moments.” Kimble, professor emeritus at the University of Wisconsin-Madison and investigator emeritus at the Howard Hughes Medical Institute, received the Thomas Hunt Morgan Medal this year in recognition of his lifetime achievements in the field of genetics.
Kimble began his work as a graduate student “with an understanding of the mystery of how organisms can develop from a single cell.” As a postdoctoral researcher at the MRC Laboratory of Molecular Biology in 1981, he found a single C. elegans The cell, called the distal tip cell, controls whether the germinal stem cells continue as stem cells or differentiate. When it killed this fragile cell, the stem cells could no longer renew themselves and began to differentiate. What Kimble discovered was the first example of a stem cell niche in any organism. That discovery set the stage for his laboratory at the University of Wisconsin-Madison, where Kimble used genetic screens for the first time to investigate how the niche regulates stem cells.
“Within a month, I saw a change in him glp-1, For germs to spread. It is noteworthy that glp-1 Mutant The phenotype was similar to killing the distal tip cell,” she says. “It was a wonderful eureka moment, a step in the door to start unlocking stem cell regulation.” The glp-1 The gene encodes a Notch receptor that is expressed in stem cells and receives signals from distal tip cells. However, understanding the regulation downstream of Notch has proven difficult.
In parallel with her stem cell niche studies, Kimble’s lab was studying germ cell fate decisions to become sperm or oocytes. His work dispelled the common belief at the time that the sperm/oocyte decision was equivalent to determining the sex of the entire organism. Starting with large-scale genetic selection, his lab identified a regulatory element in the 3′ untranslated region of a sex-determining gene and uncovered a protein that binds to that element. To his surprise, that RNA-binding protein controlled both the sperm/oocyte decision and germline self-renewal. “Who would have thought? Our cycle in cell fate decision brought us back to stem cells and brought us to the world of RNA,” says Kimble.
Over the next decades, Kimble’s team linked Notch signaling to surprising new regulators of self-renewal. After many false starts, he targeted two markers that self-renew and whose spatial extent of expression determines the size of the stem cell pool. To his surprise, those targets encode small intrinsically disordered proteins. “One of the fun things in research is deciding, ‘This is an important problem. I want to understand it,’ and then being stunned by the unexpected answers that come up,” she says.
David Greenstein, a professor of genetics, cell biology, and development at the University of Minnesota and current vice president of the GSA, says Kimble’s work “not only answered important questions, but it brought other people into the field.” What’s impressive to him is how he built “a really important and strong experimental building,” starting as a graduate student and postdoc, then in his own lab, and later through all of his trainees.
In addition to trainees in his lab, Kimble has also been instrumental in mentoring junior faculty in his department and beyond. Judy Simcox, an assistant professor of biochemistry at the University of Wisconsin-Madison, explains how influential Kimble has been to her. Kimble provided feedback on Sim Cox’s grant proposals and advice on mentoring his lab team. Maureen Barr, a distinguished professor in the genetics department at Rutgers University and current GSA secretary, began her first tenure at the University of Wisconsin-Madison in a different department than Kimble. Kimble became an ad hoc advisor to her, helping her with grant proposals and the often challenging balance between motherhood and being a scientist. She describes Kimble as “a very serious scientist with a great sense of humor.”
In addition to Kimble’s pioneering work in stem cell regulation, he has served in many leadership roles, including as GSA President in 2000 and President of the Society of Developmental Biology in 2005. She was elected to the National Academy of Sciences (NAS) in 1995 and later to the NAS Council. Under Obama, he served on the President’s Committee on the National Medal of Science, eventually chairing the committee.
“Judith’s greatness goes far beyond her prowess as a scientist or a mentor,” says Simcox. “It’s the transformative power that she has in investing in others as well as in the bigger problems that she sees.”
“I can think of no one more deserving of this Thomas Hunt Morgan Medal for all the contributions he has made to the field of developmental biology,” added Barr. C. elegansand the field of genetics as a whole.”
Congratulations to Judith Kimble on receiving the Thomas Hunt Morgan Medal for Lifetime Achievement in Genetics.
