北京大学定量生物学中心
学术报告
题 目: Lighting Up Pattern Formation Along the Central Dogma
报告人: Hernan Garcia, Ph.D.
Assistant Professor, Department of Molecular & Cell Biology and Department of Physics, University of California at Berkeley
时 间: 6月8日(周一)20:00-21:00
地 点: Online (Zoom会议ID: 915 6803 5437)
https://zoom.us/j/91568035437
主持人:刘峰 研究员
摘 要:
During embryonic development, tightly choreographed patterns of gene expression—shallow gradients, sharp steps, narrow stripes—specify
cell fates. The prediction of developmental outcomes from these
transcription factor patterns and from regulatory DNA sequence remains
an open challenge in physical biology that requires a quantitative
understanding of the mechanisms that dictate the flow of information
along the processes of the central dogma. We used stripe 2 of the even-skipped gene in Drosophila embryos
as a case study in the dissection of the regulatory forces underpinning
a key step along the developmental decision-making cascade: the
generation of cytoplasmic mRNA patterns via the control of transcription
in individual cells. Using live imaging, theoretical and computational
approaches, we developed a comprehensive toolkit to watch the regulation
of the entirety of the central dogma in real time. We found that the
transcriptional burst frequency is modulated across the stripe to
control the mean mRNA production rate. However, we discovered that
bursting alone cannot quantitatively recapitulate the formation of the
stripe, and that control of the window of time over which each nucleus
transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling led to the discovery that these two regulatory strategies—the analog control of the mean transcription rate by bursting and the binary control of the transcription time window—obey
different kinds of regulatory logic, suggesting that the stripe is
shaped by the interplay of two distinct molecular processes. Our work
provides an example of how biological numeracy can be used as a driver
for discovery as well as a stark reminder that reaching a predictive
understanding of developmental decision-making will require a precise
understanding of how gene expression is regulated not only across space,
but also over time.
报告人简介:
Hernan
G. Garcia is an assistant professor in the Departments of Molecular
& Cell Biology and of Physics at UC Berkeley. As a Physical
Biologist, his research aims to uncover the quantitative and predictive
principles dictating biological phenomena, with particular emphasis on
embryonic development. Hernan is a co-author of the textbook Physical
Biology of the Cell and a co-director of the equally named course at the
Marine Biological Laboratory in Woods Hole, MA.
Lab website: http://mcb.berkeley.edu/labs/garcia/