PhD Transfer Examination – Ian (Shen Yen) Hsu (Moses lab)

PhD Transfer Exam

Thursday December 1^st, 10:10 am – Earth Sciences Centre, Room 3087

Ian (Shen Yen) Hsu (Moses lab)

“Understanding the Evolution and Mechanism of Pulsatility”

Abstract

Several transcription factors involved in important signaling pathways have been, recently, reported to show pulsatility. This phenomenon includes unsynchronized and aperiodic promoter activation of downstream targets via rapid shuttling of transcription factors between nuclei and cytoplasm. Different from a constant nuclear localization, the dynamics of these transcription factors show pulses across time. The similarities and differences between pulsatile transcription factors (PTFs) are unclear. Although the profiles of pulses of each PTF look intuitively different from each other, in principle PTFs sharing a common signaling pathway function may have similar pulse profiles. I hypothesize that the profile of pulses can be quantified and classified to a signalling pathway function. Crz1 is a PTF that responds to a stronger calcium stress with higher pulsing frequency (1). However, the genetic circuit that encodes the intensity of environmental stress into pulsing frequency is unclear. My preliminary results suggest that vacuolar calcium transporters are involved in regulating pulse frequency, and that the localization of Crz1 is regulated by a positive feedback and then a negative feedback. To explore the circuit further, I propose to screen for genes involved in the positive and negative feedbacks. I also hypothesize that the feedbacks are mediated by only post-translational modification because Crz1 pulses with a duration within a 10-minute scale, and this hypothesis predicts that truncated Crz1 can pulse without DNA binding domains. Two motifs that are essential for Crz1 to pulse are in a disordered region, a sequence of polypeptide that does not have secondary or tertiary structure and goes through rapid evolution. Finally, I hypothesize that the intrinsically disordered region of Crz1 plays a role in Crz1 pulsatility, and I propose to ectopically express Crz1 orthologs that contain diverged disorder regions in S. cerevisiae in order to investigate how the frequency and profile of pulses is affected. This work will facilitate our understanding of the mechanism and the evolution of pulsatility.