MSc by Research: Deciphering the role(s) of Cdk1 during oocyte meiosis

About the Project

Meiosis is a specialised type of cell division that produces haploid daughter cells known as gametes that are important for sexual reproduction. Dynamic protein phosphorylation plays crucial roles during meiosis, but the mechanisms underlying the function of each kinase are not entirely clear. Cyclin-dependent kinases (CDKs) are a family of key kinases with different roles during the cell cycle. CDKs are the active kinase component of CDK/cyclin complexes. Several CDK/Cyclin complexes exist and they regulate different stages of the cell cycle. Mammals and other species such as nematodes possess an array of CDKs to carry out a range of cell cycle activities. One member of the family, CDK-1, is highly conserved among eukaryotes and a primary regulator of mitotic progression. Additionally, CDK-1 was found to be essential for embryonic development as well as meiotic oocyte resumption in mice. These results align with a study in the nematode *C. elegans*where CDK-1 was discovered to be vital for meiotic progression to metaphase I. Despite these results, little is known about the precise roles CDK-1 plays during oocyte meiosis and dissecting the specific roles and timing of CDK-1 kinase activity during meiosis remains an important unanswered question. The use of conventional, chronic deletion/depletion strategies (knockout and RNAi) are not suited to address CDK-1’s roles during chromosome segregation because CDK-1 regulates meiotic events in prophase in mouse and *C. elegans*oocytes. While the use of the classic CDK-1 inhibitor RO-3306 has given more insight into the requirement for Cdk1 activity during cell division, RO-3306 can inhibit other kinases, such as Cdk2, at fairly low concentrations. Hence, the main question we aim to answer is 1) what are the specific roles of Cdk1 during chromosome segregation in oocytes?

To this end, a means to acutely deplete or inhibit Cdk1. My lab has experience with three complementary methodologies: 1) Auxin-induced degradation (AID); 2) temperature-sensitive (ts) alleles; and 3) analogue-sensitive (as) alleles (a.k.a. chemical genetics). These methods overcome the problems of traditional RNAi-mediated depletion, with AID achieving protein degradation within minutes/hours, fast-acting ts alleles inhibiting function in minutes, and asalleles achieving inhibition virtually instantly. We will then investigate what cyclins are important for each of the functions. All B-type cyclins have non-overlapping functions during oocyte meiosis, but what these functions are remains unknown. Thus, the second question is 2) what are the different cyclins associated with Cdk1 function(s) in oocyte meiosis?

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Life Sciences MSc by Research MSc by Research (Postgraduate) : Study : University of Dundee

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Biological Sciences (4)