Paula Cohen, professor of genetics in the College of Veterinary Medicine, has won a $100,000 grant from the Bill & Melinda Gates Foundation to develop a radical approach to contraception – an area that has remained static for many years.
"That's what's truly innovative here: We are targeting a stage in the reproductive cycle that's poorly understood," Cohen said.
Cohen's project will look at meiosis, a poorly understood stage of development in which a sperm cell's DNA is halved. When the sperm fertilizes an egg – which also contains only one half of its chromosomes – the resulting embryo is restored to the full number of chromosomes.
"I've always thought that if we can stop those cells from actually getting into meiosis, you'd have a really good contraceptive," Cohen said.
Her new approach, centering on the sperm cell's entry into meiosis, before it even leaves the testis, offers several benefits.
For example, should one sperm sneak its way through to meiosis, the "surveillance machinery" present during meiosis would get rid of that solitary cell; in other words, the meiotic process itself would "check" for escapers. And unlike later stages of sperm cell development, the cell's entry into meiosis is accessible to blood-borne factors such as drugs.
"The problem is, we know very little about meiosis, because it's a very hard stage to target biologically or molecularly," she said. "Only recently have we started to gather the tools to be able to look at it." One tool Cohen will use is called CRISPR/Cas9, a genome editing technology that allows genes to be modified permanently and very rapidly.
She has three goals. First, she'll try to prove she can get the sperm cells to go into meiosis in culture. Second, she'll monitor the cells' entry, by engineering what are known as reporter mice, whose cells turn green or red depending on whether or not they have entered meiosis. Third, and as proof-of-principle, she'll try to manipulate two genes that are known to affect a cell's entry into meiosis.
One gene is required for sperm stem cell maintenance in the testes; if it is deleted, cells rapidly progress into meiosis. The second gene is required for the sperm cell to enter meiosis; it if is blocked, the cells stop developing. "So we've got a gene that should accelerate their entry into meiosis and one that should slow it down," Cohen said.