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C. elegans projects

Meiotically dividing spermatocytes

Understanding the interplay between the cell cycle and cell differentiation pathways

Cell division is one of the most fundamental processes of life, and the core molecular mechanisms that guide cells through the cellular events of growth, DNA replication, and division into two daughter cells are evolutionarily conserved from yeast to humans.  However while we now understand the basics of this core program, we know much less about the ways that the core cycle is modified and regulated by cell specific factors. In the Shakes’ lab we are exploring the following question…

How is the meiotic cell cycle that gives rise to sperm and oocytes coordinated with the distinct developmental programs that give rise to either large, nutrient rich oocytes or small, motile sperm?

MSP (green) being packaged into fibrous bodies

How to build a functional sperm cell

By design, sperm cells are small, motile, and transcriptionally inactive. Thus a key step in the developmental program of making a sperm involves prepackaging components that need to be synthesized before the turnoff of transcription and stored for later use. Nematode spermatogenesis provides an extreme example of this process; bulk transcription ceases prior to the meiotic divisions and translation ceases immediately after anaphase II. In particular, spermatocytes must synthesize and prepackage a small filament forming protein called the major sperm protein (MSP). Within mature nematode sperm, MSP serves both as the protein that drives sperm motility and as a signaling protein that triggers oocyte maturation and the physical process of ovulation. Some of the questions that we are currently exploring include…

Once a germ cell has committed to being a spermatocyte rather than an oocyte, what transcription factors and post-translational modifiers implement the spermatogenesis program – and make sure that the “roll-out” is successful?

How is it that the major sperm protein (MSP) can assemble into large stable fibrous bodies within spermatocytes but later undergo dynamic polymerization within the pseudopods of crawling spermatozoa?

Crawling nematode sperm

How are sperm able to find and crawl to an egg – in the absence of either transcription or translation?