Description of the PhD thesis project
One of the most remarkable properties of developing
multicellular systems is their ability to generate precise outcomes, e.g., cell
fate patterns of morphogenetic events, even in the face of considerable
fluctuations in their environment. To maintain developmental precision,
organisms have evolved molecular mechanisms to change and adjust their
developmental rates or even arrest development and resume at later time points.
Combining microscopy, image analysis, mathematical modeling and genetics, our
group investigates how this kind of robustness emerges during development,
using C. elegans as a model organism with powerful genetics,
genome-editing, and live-imaging tools.
In this PhD project, we will focus on the
development and cell-fate specification of hypodermal stem cells. Using
real-time live-imaging of transcription as well as transcription factor
dynamics, we will try to uncover how the underlying gene regulatory networks achieve
an invariant stem-cell fate-progression over a wide range of temperatures.
International, interdisciplinary &
intersectoral aspects of the project
All projects in
the lab run at the interface between developmental biology and biophysics with
strong emphasis on interdisciplinarity. This project will be developed in close
collaboration with the group of Christopher M. Hammell at Cold-Spring Harbor
Laboratories which will provide expertise in genetics, biochemistry, and genome
engineering. Several lab visits and joint retreats with this group are planned.
mathematical and computational methods for modeling cell-fate decisions, we
collaborate with groups at Rockefeller University New York City as well as
groups in Paris, France.
- Brian Kinney, Shubham Sahu,
Natalia Stec, Kelly Hills-Muckey, Dexter W. Adams, Jing Wang, Matt Jaremako,
Leemor Joshua-Tor, Wolfgang Keil*, Christopher M. Hammell*. Circadian
rhythm orthologs drive pulses of heterochronic miRNA transcription in C.
elegans. bioRxiv (2022)
- Natalia Stec,
Katja Doerfel, Kelly Hills-Muckey, Victoria M. Ettorre, Sevinc Ercan, Wolfgang
Keil*, Christopher M. Hammell*. An Epigenetic Priming Mechanism Mediated by
Nutrient Sensing Regulates Transcriptional Output during C. elegans
Development. Current Biology (2021)
- Michelle A.
Wolfgang Keil*, Justin M. Benavidez, Iva Greenwald. HLH-2/E2A
Expression Links Stochastic and Deterministic Elements of a Cell Fate Decision
during C. elegans Gonadogenesis. Current Biology (2019)
- Wolfgang Keil, Lena M. Kutscher, Shai Shaham, Eric D. Siggia. Long-Term
High-Resolution Imaging of Developing C. elegans Larvae with Microfluidics. Developmental Cell (2017)
M. Kutscher, Wolfgang
Keil, Shai Shaham. RAB-35 and ARF-6 GTPases
Mediate Engulfment and Clearance Following Linker Cell-Type Death.
Developmental Cell (2018).