K.Athryn Anderson, a developmental biologist at Memorial Sloan Kettering Cancer Center who is known for her work on the genetics of early embryogenesis, died November 30th at the age of 68.
During her scientific career, Anderson used rigorous genetic screening assays to identify mutations that are suspected of disrupting cell division and differentiation in model systems. After identifying a gene of interest, she turned to a technique known as forward genetics and created model organisms such as fruit flies and mice with a specific phenotype to better understand the molecular basis. With these tools, Anderson made important contributions to the scientists’ understanding of various genetic pathways – particularly the Toll and Hedgehog pathways – that are required for the proper development of these animals.
“Kathryn was fearless and very open-minded,” said Tatiana Omelchenko, a senior scientist at Anderson’s laboratory, who uses confocal microscopy to image live mouse embryos The scientist. “Each lab has its own setting and mood, and when you walked into Kathryn’s lab, you immediately felt very focused.”
Anderson was born in La Jolla, California, in 1952 and became interested in science from an early age LIFE This included a detailed picture of a human fetus, according to an interview published shortly after her death. She attended the University of California at Berkeley, where she received her bachelor’s degree in biochemistry, before joining a graduate school in neurodevelopment at Stanford University in 1973.
Anderson dropped out of that program after just two years, earned a Masters in Neuroscience, and spent the next several years searching for her scientific niche. She enrolled briefly in the University of California Medical School at San Diego, an experience that led her to realize her love of basic research. “The clinical work wasn’t my thing,” said Anderson in a 2005 biography. “I felt most comfortable in the laboratory.”
Ultimately, Anderson ended up at the University of California at Los Angeles and studied developmental genetics from Drosophila under the direction of the biologist Judith Lengyel. For her doctoral thesis, Anderson showed that in the first two hours after fertilization, the development of Drosophila Embryos remain under maternal control, with maternal RNA and proteins directing cell division and differentiation within the egg.
In order to advance her study of fruit flies, Anderson traveled as a postdoc to the Max Planck Institute for Developmental Biology in Germany Drosophila Geneticist Christiane Nüsslein-Volhard. In 1995, Nüsslein-Volhard received a Nobel Prize for her work on mass screenings to identify mutations that disrupt embryonic development, and Anderson would continue studying a handful of the genes identified in those early screenings throughout her career.
One such gene, known as tollIt turned out to play an important role in dorsal-to-ventral (DV) differentiation – as Anderson said in her biography, dictates how a fly embryo “knows its back from the abdomen”. In addition to checking the function of Toll, Anderson continued to expand on the wider toll road after returning to the University of California at Berkeley as an assistant professor in 1985 and later in her own laboratory at the Sloan Kettering Institute, which she opened at Memorial Sloan Kettering in 1996. During that time, Anderson and her team identified about a dozen genes involved in cell differentiation along the DV axis, and they used similar screening methods to better understand Toll’s role in innate immunity from Drosophila. Their results were noted by geneticists Jules Hoffmann and Bruce Beutler, whose study of toll-like receptors in both the fruit fly and mammalian immunity later earned them a Nobel Prize.
Memorial Sloan Kettering Cancer Center
After her successes with fruit flies, Anderson began thinking about applying her same methods to studying mice. She spent a year on sabbatical in Rosa Beddington’s laboratory at the National Institute for Medical Research in the UK, where she demonstrated that Toll does not play an analogous role in mammalian DV differentiation. It showed, she said in a 2016 interview with developmentthat “there are things about early mammalian development that cannot be extrapolated from flies.”
Back at the Sloan Kettering Institute, Anderson began again with mass genetic screenings to identify mutations of interest in mice and then examine them in detail. These were lengthy experiments that often took years to produce results. “I think their main contribution is to discover the functions and roles of genes through this mutagenesis screen,” says Omelchenko. “That’s amazing because. . . The mouse embryo model is pretty complex, but she did the job. “
Anderson and her team examined more than 12,000 mutations and selected about 40 that cause apparent phenotypic disorders in mid-pregnancy. Anderson worked diligently for many years, identifying previously unknown avenues that have since led to new directions in research in the field of developmental biology.
For example, through her screening, Anderson identified a previously unknown relationship between cilia – microscopic, hair-like structures on the outside of some cells – and the proper signaling of the Hedgehog signaling pathway, which determines cell differentiation in mammalian embryos. Further research showed that components of this pathway are enriched in cilia, while mice with certain mutations in genes involved in hedgehog signaling lacked cilia in a structure known as a node that controls gastrulation in vertebrate embryos. “It actually turned out to be pretty amazing: there is this whole organelle that is needed for hedgehog signaling in vertebrates, but not in flies,” Anderson said in her development Interview. “It’s a geneticist’s dream, but it begs the question of why the genome is organized this way: There are so many weak spots in hedgehog signaling – and hedgehog is so important.”
For her contributions in the field of developmental biology, Anderson was inducted into the National Academy of Sciences in 2002 and elected to the National Academies’ Institute of Medicine in 2008. She also received the Thomas Hunt Morgan Medal for Lifelong Contributions to the Science of Genetics in 2012, the Excellence in Science Award from the Federation of American Societies for Experimental Biology in 2014, and the Edwin G. Conklin Medal from the Society for Developmental Biology im Year 2016 for outstanding and sustainable research in 2016 among others.
Prior to her death, Anderson had discussed the possible expansion of her research into human genetics, as disorders in hedgehog signaling have since been linked to both birth defects and a range of diseases known as ciliopathies. However, it was a question that she wanted to leave to other scientists to continue her methodological work on studying mutations in mice.
“A lot of scientists are very quiet people, but in today’s society you have to be very loud [so] that people listen to you, ”says Omelchenko. “Kathryn is a great example of being calm, thinking very deeply, and at the same time becoming a very successful and bright scientist. I think I will continue to learn from her even though she died. “
Anderson is survived by her husband, Timothy Bestor, a Columbia University geneticist.