Kathryn V. Anderson awarded FASEB Excellence in Science Award

By Marsha E. Lucas

Kathryn V. Anderson of the Sloan-Kettering Institute was selected to receive the 2014 Federation of American Societies for Experimental Biology (FASEB) Excellence in Science Award. This award recognizes the outstanding achievements of women in the biological sciences who have made significant contributions to their scientific discipline.

Anderson has greatly contributed to our understanding of mechanisms underlying the development of both vertebrate and invertebrate species. In her classic work she identified Toll as a maternal effect gene essential in establishing the dorsal-ventral body plan in Drosophila. She went on to establishing a link between Toll signaling and innate immunity which laid the groundwork for others like Jules Hoffman who won the Nobel Prize in 2010 for his work on innate immunity. Anderson has discovered some of the fundamental features of mammalian development by taking a fly geneticist approach--conducting forward genetic screens in mice. She has identified new genes critical in major developmental processes including morphogenesis, axis specification, and cell signaling.

Anderson began her doctoral training in 1977 at the University of California, Los Angeles with Judith Lengyel studying RNA synthesis in the developing fly embryo. At the time there were few women faculty members in the department.

“It was really important to have women as role models,” Anderson said in a recent interview. “[Lengyel] was tough and full of energy and a good model,” she said.

In 1981, Anderson joined Christiane Nüsslein-Volhard's lab at the Max Planck Institute in Germany for her postdoctoral training where her journey with Toll began. Nüsslein-Volhard and Eric Wieschaus were doing large-scale screens for genes that affected fly development which earned them the 1995 Nobel Prize in Physiology or Medicine.

“The interesting thing about [Toll] is how the project morphed over time,” she said. “I think that's what happens when you start with genetics—it takes you places you can't predict.”

Loss of function Drosophila Toll mutant embryos lack ventral structures. One of the greatest moments of Anderson's career occurred while conducting cytoplasmic injection experiments to rescue mutants with defective dorsal-ventral body plan specification. Normally, wild type cytoplasm injected into dorsal-ventral mutants rescued the phenotype, but did not change the polarity of the embryo (i.e., which side would be dorsal and which side would be ventral). However, when Toll^- mutants were injected with wild type cytoplasm, the location of the injection determined the ventral side of the embryo.

“It was amazing just to watch embryos gastrulate [in] a new orientation that I could define by where I put my needle,” she said. “Knowing that in that needle there was a molecule that was controlling embryonic polarity was really exciting.”

Identifying that molecule became the focus for Anderson as she started her own lab at the University of California, Berkeley in 1985. It was a “huge surprise” to learn Toll was a transmembrane receptor as it went against conventional wisdom of how maternal components control early development, she said. “Having a transmembrane protein was really a shift in the way we were thinking about what this pathway might do.”

Her group worked out many components of the Toll pathway in flies and soon became interested in whether it was evolutionarily conserved. A sabbatical with Rosa Beddington in 1993 at the National Institute for Medical Research in London offered her an opportunity to learn mouse embryology and explore whether Toll played a role in early mouse development. “I really fell in love with the mouse embryo because Rosa Beddington was not afraid to do anything with a mouse embryo,” she said.

“It became apparent at that time that Toll had nothing to do with patterning in early vertebrate development and instead that there was a conserved function of Toll but it was in immune responses,” she said.

Anderson went on to take a genetic approach to studying innate immunity in flies, but the story in mouse got her thinking that “there might be things about vertebrate development that you [can not] extrapolate from fly development.”

She became convinced that a phenotype based screen could be carried out in the early mouse embryo. “It seemed like you should be able to induce mutations at a high enough frequency that you would hit genes of interest without screening thousands of mice, and the genomic infrastructure was there ... to map them and ultimately identify the gene responsible.”

The second big highlight of Anderson's career came when her graduate student Andrew Kasarskis discovered a clear mutant in Mendelian ratios after screening only his fourth or fifth mouse litter. What she saw through the microscope “made it clear that this was going to work and that the phenotypes were going to be interesting,” she said.

In that first small screen they identified an allele of Smoothened—which had not been previously cloned. They also identified an allele of Rab23—a negative regulator of the Sonic hedgehog pathway—which led to many discoveries of processes required for vertebrate hedgehog signaling that are not required in flies.

“The theme of modern developmental biology has been about conservation,” Anderson said. “But, the theme of my career has been about divergence.”

In 1996, Anderson moved her lab to the Sloan-Kettering Institute where she currently chairs the Developmental Biology Program. She mentors students, postdocs, and young faculty. Her idea of mentoring is “working together with someone toward a common goal.”

She explained, “I give people a lot of freedom, ... but I'm always there to help if they need it.”

Anderson is a fellow of the American Association for the Advancement of Science and the American Academy of Arts and Sciences. She is a member of the National Academy of Sciences, as well as a former President of the Society for Developmental Biology (1998-1999).

The FASEB Excellence in Science award includes an unrestricted research grant of $10,000. Anderson will deliver her awards lecture at the 2014 SDB Annual Meeting (July 17-21), at the University of Washington, Seattle.