When Judith Kimble began studying animal development in the nematode Caenorhabditis elegans, she 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 lucky that approach led to a career.” Her “black box” focus led Kimble to groundbreaking discoveries, many of which came with “eureka moments.” Kimble, an emeritus professor at University of Wisconsin-Madison and emeritus investigator at Howard Hughes Medical Institute, received the Thomas Hunt Morgan Medal this year to recognize her lifetime achievements in the field of genetics.

Kimble started her work as a graduate student with the goal of understanding “the mystery of how a creature could develop from a single cell.” In 1981 as a postdoctoral researcher at MRC Laboratory of Molecular Biology, she found a single C. elegans cell,called the Distal Tip Cell, controls whether germline stem cells continue as stem cells or differentiate. When she killed that critical cell, stem cells could no longer self-renew and started to differentiate. What Kimble had discovered was the first example of a stem cell niche in any organism. That discovery set the stage for her lab at the University of Wisconsin-Madison, where Kimble first used genetic screens to investigate how the niche regulates stem cells. 

“Within a month, I found mutations in glp-1, for germline proliferation. Remarkably, the glp-1 mutant phenotype was the same as killing the Distal Tip Cell,” she says. “That was a wonderful eureka moment, a foot in the door to start unraveling stem cell regulation.” The glp-1 gene encodes a Notch receptor that is expressed in stem cells and receives signals from the Distal Tip Cell. However, understanding regulation downstream of Notch proved challenging. 

In parallel to her stem cell niche studies, Kimble’s lab was studying the germline cell fate decision to become sperm or oocyte. Her work upended the then-common belief that the sperm/oocyte decision was equivalent to sex determination of the entire organism. Starting from large scale genetic selections, her lab identified a regulatory element in the 3′ untranslated region of a sex determination gene and uncovered proteins that bind to the element. To her surprise, those RNA-binding proteins controlled both the sperm/oocyte decision and germline self-renewal. “Who would have thought? Our detour into a cell fate decision brought us right back to stem cells and launched us into the RNA world,” Kimble says.

Over the next decades, Kimble’s team connected Notch signalingto surprising new regulators of self-renewal. After many false starts, she honed in on two Notch targets that drive self-renewal and whose spatial extent of expression determines the size of the stem cell pool. To her surprise, those targets encode small intrinsically disordered proteins. “One of the fun things in research is to decide ‘this is an important problem. I want to understand it’ and then to be stunned by the unexpected answers that fall out,” she says.  

David Greenstein, a professor of genetics, cell biology, and development at the University of Minnesota and current GSA Vice President, says that Kimble’s work “not only answered important questions, but it brought other people into the field.” What’s impressive to him is how she built “a really important and robust experimental edifice,” starting as a graduate student and postdoc, then in her own lab, and later through all her trainees.

In addition to trainees in her own lab, Kimble has also played a significant role mentoring junior faculty in her department and beyond. Judi Simcox, an assistant professor of biochemistry at University of Wisconsin-Madison, shares how influential Kimble has been for her. Kimble gave feedback on Simcox’s grant proposals and advice on mentoring her lab team. Maureen Barr, a distinguished professor in the department of genetics at Rutgers University and current GSA Secretary, began her first tenure track position at the University of Wisconsin-Madison in a different department from Kimble. Kimble became an ad hoc advisor for her, helping her navigate grant proposals and the often-challenging balance between motherhood and being a scientist. She describes Kimble as “a very serious scientist who has a great sense of humor.”

In addition to Kimble’s pioneering work in stem cell regulation, she has served many leadership roles 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 elected to the NAS council. Under Obama, she served on the President’s Committee of the National Medal of Science, and ultimately chaired the committee.

“The greatness of Judith is so far beyond her brilliance as a scientist or her brilliance as a mentor,” says Simcox. “It is the transformational power she has through investing in others as well as in big problems that she sees.”

Barr adds, “I cannot think of someone who deserves this Thomas Hunt Morgan Medal more for all the contributions that she’s had in the field of developmental biology, the field of C. elegans, and the field of genetics as a whole.”

Big congratulations to Judith Kimble on receiving the Thomas Hunt Morgan Medal for her lifetime achievements in genetics.

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