Harvard University COVID-19 updates

Department News

POSTDOC PROFILE: ANTJE FISCHER [MANGO LAB]

POSTDOC PROFILE: ANTJE FISCHER [MANGO LAB]

Antje Fischer never outgrew her childhood desire to be a veterinarian. For as long as she can remember she chased insects and watched any animal documentary she could get her hands on. Fortunately for MCB, as it turns out, during a veterinary internship as a teenager in her hometown of Berlin (Germany, not Ohio), she discovered she hadn’t the heart for the grimmer aspects of that occupation (“To this day I still feel bad for burning nematodes when we handle our worms,” she mourns). So, accustomed to clarifying concepts for her peers in high school biology class, she figured,  “Why not make a living out of explaining everything?” and attended the Free University of Berlin planning to become a biology teacher.

At University, however, she found that the teaching track fell short of satisfying her scientific curiosity, so, halfway through her first year of college, she determined she would pursue a PhD. In the meantime, she worked in a subgroup of Walter Sudhaus’s lab headed by Christian Fischer (no relation), where she observed and documented grooming movements in a variety of insect species over several weeks. By comparing the behavior among species they identified traits that appeared to be evolutionarily conserved and others that might have been modified into new behaviors involved in brood care and mating behavior.  “It was the most low-cost research you could possibly imagine,” she laughs, “we would collect animals from our neighborhood, we even got silverfish from the bathroom.”

She completed her thesis with Gerhard Scholtz at the Humboldt University of Berlin before heading to the European Molecular Biology Laboratory (EMBL) in Heidelberg to study among geneticists, structural and molecular biologists, folks who “can distinguish a mouse from a nematode but that’s pretty much it.”

Besides the harsh reality that careers in classical zoology and evolutionary biology are dwindling, Fischer sought a doctorate in molecular biology in order to answer the “hows” of evolutionary biology. “It’s only a very small step from ‘how could this structure evolve’ to ‘how does this structure develop,’” she notes. “All the changes that we see as a ‘read-out ‘of evolution ultimately happen on the level of DNA  (often just some small mutation)—it’s the genes and their regulation that are changing and that’s what underlies most changes in morphology.” Genetics and evolutionary biology are increasingly inseparable.

The only other zoologist in her EMBL lab was the P.I., Detlev Arendt, with whom she studied the annelid Platynereis dumerilii, which she characterizes as “a little bit like an earthworm with fur, living in the ocean.” (Apparently, “when they’re three days old they look like little gummi bears.”) Applying her training in zoology and morphology, Fischer first compiled an “atlas” of Platynereis development. She then focused on analyzing the development of the mesoderm to show that Platynereis exhibits characteristics otherwise only found in insects. Thus, these features had already been present in the last common ancestor of insects and Platynereis, around 550M years ago.

As a graduate student, Fischer attended the Woods Hole Marine Biological Laboratory (MBL) embryology course, an intensive six-week crash course on a wide variety of model organisms from mice to flies to “weird marine creatures.” Over the course of these six weeks, her first in the United States, Fischer encountered an American can-do spirit that complemented her German pragmatism. Keen to explore social networks outside the cozy European evo-devo community, she followed her doctoral degree with a 2.5-year postdoc at MBL, where she worked with Joel Smith and enjoyed TA-ing the same embryology course that brought her to Woods Hole in the first place.

As her first postdoctoral project, Fischer studied the gene regulatory network underlying the early development of the sea anemone Nematostella vectensis. Fischer also worked with ctenophores, or comb jellies, which might be one of the oldest animal groups on earth. In collaboration with researchers who visit the MBL regularly during the summer, she investigated the peculiar cell fate determination mechanisms in ctenophores (elucidated in an EvoDevo article here) and helped to build a developmental expression profile with the MBL embryology course.

After choosing her first postdoc for its organisms—Cnidarians—she sought a more mechanism-driven developmental biology lab for her second. Susan Mango’s lab uses the well-established model system C. elegans, which affords an ample array of available tools and resources, in contrast to the limited options offered by more unusual organisms at the MBL. Since joining the Mango lab as a postdoc last winter, Fischer’s not the only one who has benefitted from the arrangement; According to Susan Mango, “Antje is taking the lab in exciting new directions—she’s working on a mysterious, conserved regulatory protein, and she’s initiating her studies in mammals as well as C. elegans.”

Fischer’s current research concerns the regulation of pha-4 aka FoxA – a highly conserved developmental gene indispensible for developing a foregut and hindgut in most animals. The expression of FoxA is tightly regulated and potentially conserved across the animal kingdom. A loss or gain of FoxA function can alter the fate of a cell and thus promote tumor formation and cancer progression. In humans, for example, the deregulation of FoxA1 has been particularly associated with breast cancer. Thus, understanding the regulation of FoxA might help to identify new specific targets for cancer therapeutics.

Shortly after joining the lab, Fischer earned a fellowship from the German Research Foundation, or DFG.  The grant itself is dispensed in euros; “It’s the first time in my life that my salary depends on the currency exchange,” she jokes. Fischer attributes the success of her multilateral project to its versatile appeal; “I feel the project has something for everyone,” she campaigns, “it has the FoxA for Susan, it has the cancer part for the funding agencies, and it has the evolutionary part for me!” Of course, her playful plug is in part facetious, but it is hard to secure funding for evo-devo research.

“Evo-devo is always idealistic research,” she concedes, “you do it because you are interested and you are curious and you want to work with strange animals…but understanding evolution is hard to sell.” Both her postdoctoral experiences have obliged her to face this reality, but she’s grateful for becoming “a little more realistic and a little less naïve.” While C. elegans are perhaps not as elegant as ctenophores (which “look like little U.F.Os swimming through the sea”), with a well-established model organism, “you can understand mechanisms so much better than trying to do that in an animal where so many tools are still lacking.” Despite her animal-lover’s passion for all creatures quirky and bizarre, she’s realized that “taking advantage of these more established models can also answer really cool questions and maybe it’s easier to go from these well established models into the little oddballs and study those in addition than trying to do it the other way around.”

This seasoned pragmatism in no way compromises Fischer’s intrepid enthusiasm for discovery. As Mango attests, “Her fearlessness extends beyond the lab; Antje lead us up a mountain during our spring retreat in the Berkshires.” Whether in the lab or on the trail, collaborating with Fischer “has been fun and inspiring.”

Fischer modestly contests Mango’s version of events on that mountain (“I didn’t even have a map,” she recalls). When not allegedly trudging up the craggy peaks of New England, Fischer enjoys diverse hobbies including photography, horseback riding, and bread making.  Prior to graduate school, she was an avid equestrian and owned her own horse—Pajonn, after the Sami god of Thunder—but surrendered that passion to pursue her career. She regrets the loss, but admits that keeping a horse in Cambridge would be virtually impossible (if an inventive means to bypass rush hour on the T).

While Fischer looks forward to running her own lab in future, either here in the United States or back in Germany, part of her will miss being a postdoc: “I love doing bench work as much as I love designing experiments and analyzing data. Being a postdoc is a great learning experience. You get to develop your scientific independence and learn to supervise younger scientists while still having an experienced PI with whom to discuss ideas and focus.”

She advises postdocs-to-be and young scientists everywhere, “don’t underestimate yourself.” Having strayed so far from where she started, from animal grooming to nematode genetics, she encourages others to be open-minded and to “seize any opportunity you might face.” Regardless of whether you succeed in the way you expected to succeed, “you grow with the challenge.”
      
For more on Antje Fischer’s research throughout her career, see her PubMed page here.

You might also read a piece Antje just published in Die Zeit online.

View Susan Mango’s Faculty Profile