Paula Cohen of Cornell University in the U.S. will develop a spermatogonial stem cell culture system to investigate whether the first stage of sperm formation - meiotic division of the spermatogonial cell - is a valuable target for the development of effective male contraceptives. Targeting this early stage rather than later stages has several advantages including that it is accessible to compounds in the circulation, and that the effect on fertility would be rapid and reversible. However, little is known about the molecular mechanisms regulating meiotic entry. They will develop a spermatogonial stem cell culture system carrying fluorescent reporter proteins that signal cell state and meiotic entry. They will then use CRISPR/Cas9 genome editing to mutate genes known to be involved in meiotic entry and stem cell maintenance to test the system, and use CRISPR interference to test the effect of switching one of those gene off and then back on again on the spermatogonial stem cells. Once the system has been set up, it can be used to screen for new genes involved in meiotic entry that would be good candidates for the development of novel male contraceptives.
More information about Develop Novel Platforms to Accelerate Contraceptive Drug Discovery (Round 18)