Phoebe is originally from Taiwan. She grew up in Hsinchu, a northern city which is famous for her all-year-round wind in Taiwan. She later moved to Taipei for her undergraduate and master studies. As an undergraduate student in National Yang-Ming University, she worked in the lab of Dr. Gwo-Jen Liaw to study transcriptional regulation during fly embryogenesis. For her master training, she joined the lab of Dr. Jun-Yi Leu in Academia Sinica, where she used budding yeast as a model system to dissect the molecular mechanisms by which a chaperone protein, Hsp90, buffers phenotypic consequences from genetic or non-genetic variations¹. Phoebe’s research experiences in the Leu lab sparked her interest in evolution. She decided to go abroad for an advanced training in understanding biology via both molecular and evolutionary perspectives.

Phoebe conducted her doctoral research in the lab of Dr. Andrew Murray at Harvard University. With the power of yeast genetics and experimental evolution, her doctoral work addressed how a novel biological function arises in evolution. A biological function, such as chromosome replication or segregation, is the result of a group of collectively acting proteins and is often modified or innovated in evolution. Phoebe focused on chromosome segregation and two anciently duplicated kleisin proteins that determine mitosis or meiosis separately in eukaryotes. She evolved budding yeast cells to use the meiotic kleisin for mitosis and asked which mutations, either in the meiotic kleisin or elsewhere of the yeast genome, allow cells to adapt the meiotic kleisin to a modified biological function (mitosis). She discovered that most of mutations are outside of the meiotic kleisin, especially in proteins of functional modules that don’t directly participate in chromosome segregation². Her work suggests that genetic targets for altering a conserved biological function during evolution are not restricted to the known proteins that directly participate in that function. Her doctoral work is one of important studies that pioneer the concept of “evolutionary repair³.”

Microbes often live in a crowd with other microbial species and compete for limited nutrients or space. In order to survive, microbial species deploy various strategies to co-operate with their neighbors or antagonize them. In the Malik lab, Phoebe is interested in understanding the antagonism between fungi and bacteria. She is applying experimental evolution to understand how microbes adapt to the selection pressure imposed by other antagonistic species and biological consequences of the co-evolution between two antagonistic species. This approach will yield critical insights into novel targets and molecular mechanisms of genetic conflict in the microbial world.

In her spare time, Phoebe enjoys cooking, making pottery, jogging, swimming, and reading. Phoebe likes water a lot; living in Seattle has been very pleasant to her as she enjoys tranquil and expansive views when jogging around the waterfronts.

Click here for Phoebe Hsieh's curriculum vitae

Publications

Research Publications:

1. Hsieh, Y. -Y., Sun, W., Young, J. M., Cheung R., Hogan, D. A., Dandekar, A. A., Malik, H. S. (2024)

“Widespread fungal-bacterial competition for magnesium lowers bacterial susceptibility to polymyxin antibiotics” PLOS Biology DOI: 10.1371/journal.pbio.3002694

2. Hsieh, Y. -Y., O’Keefe, I., Sun, W., Wang, Z. C., Vu, L., Ernst, R., Dandekar, A. A., Malik, H. S.

(2024) “A novel PhoPQ-potentiated mechanism of colistin resistance impairs membrane integrity in

Pseudomonas aeruginosa” BioRxiv preprint DOI: 10.1101/2024.10.15.618514

Hsieh-CV 13. Hsieh, Y. -Y., Makrantoni, V., Robertson D., Marston, A. L., Murray, A. W. (2020)

“Evolutionary repair: changes in multiple functional modules allow meiotic cohesin to support mitosis.”

PLOS Biology 18(3): e3000635 DOI: 10.1371/journal.pbio.3000635

4. LaBar T., Hsieh, Y. -Y., Fumasoni M., Murray, A. W. (2020) “Evolutionary repair experiments as a

5. window to the molecular diversity.” Current Biology 30: R565-R574 DOI:10.1016/j.cub.2020.03.046

Hsieh, Y.-Y., Hung, P.-H., Leu, J-Y. (2013) “Hsp90 regulates non-genetic variation in response to

environmental stress.” Molecular Cell 50: 82–92 DOI: 10.1016/j.molcel.2013.01.026

6. McDonald, M.J., Hsieh, Y.-Y., Yu, Y.-H., Chang, S.-L. and Leu, J.-Y. (2012) “The evolution of

low mutation rates in experimental mutator populations of Saccharomyces cerevisiae.” Current

Biology 22: 1235–1240 DOI: 10.1016/j.cub.2012.04.056

Publication in revision:

7. Hsieh, Y. -Y., Dandekar, A. A., Malik, H. S. (2023) “Trans-kingdom competition between fungi

and bacteria” (Review, revision being prepared for mBio)