The Schedl Lab led by Dr. Tim Schedl recently received NIGMS R35 grant. The grant provides funding for studying “control of germline stem cells and the switch to meiotic development in C. elegans” for 5 years.
This grant is to study the switch from stem cells to early meiotic prophase (leptotene) cells, which is regulated largely through post-transcriptional control mechanisms, translational repression and protein degradation.
One part of this work, conducted by staff scientist Dr. Ariz Mohammad, is to determine how the SCFprom-1 substrate specific protein degradation complex stops mitotic cell cycling and promotes homologous chromosome pairing and meiotic recombination. These processes need to be repressed in stem cells and activated for meiotic entry.
The other part of this work, conducted by staff scientist Dr. Jian Chen, arises from the extensive translational repression in germ cells, is to identify genome-wide the genes that are translated in stem cells and not early meiotic prophase cells and, conversely, the genes that are translated in early meiotic cells and not in stem cells, using ribosome pull-downs and RNA-seq. However, the germline tissue contains all stages of germ cell development, from stem cells to mature gametes, complicating genome-wide analysis. Therefore, Jian has developed a genetic system where all the germ cells are stem cells, that can then be switched to early meiotic prophase cells, using auxin induced degradation of a key stem cell fate regulator, to facilitate genome-wide assessment of translation status.
To learn more, visit Schedl Lab.