EastBio: Defining the role of intercellular microtubule-based transport in germ cells and fertility

Germline cells throughout metazoans are connected together in a cyst through intercellular bridges, made of microtubules and stabilized by a channel protein structure. In female germ cells, the bridges facilitate transport of resources from the nurse cells to the oocyte. Little is known about the material exchange across these bridges in male germ cells, although the absence of intercellular bridges is associated with defects in spermatogenesis and infertility. The project aims to understand how material exchange takes place across the intercellular bridges at the molecular level and define the nature of material exchange.

This student will work with spermatogonial stem cells, which have these intercellular bridges connecting cells together, as a model system. They will use expansion microscopy to image and obtain super-resolution quantitative data on the bridges such as number of microtubules in the bridge, bridge size and microtubule orientation. The student will then establish assays to test whether diffusion or microtubule-based transport are the dominating exchange mechanism between cells using photoconvertible fluorophores and microscopy. They will identify which motors are responsible for transport, what molecules are transported, and define the molecular requirements for material exchange using cutting-edge proteomics, single cell studies and cell biology approaches. The student will then develop functional studies to interfere with material exchange and analyze the consequences for male germ cells. 

Finally, the student would also have the opportunity to use coarse-grained molecular dynamics simulations to compare with the acquired experimental measurements, which will illuminate the mechanics of the bridge and intercellular transport. Explicitly simulated vesicles will diffuse through the intercellular bridge, as well as kinetical bind/unbind to microtubules and be actively transported. These models will provide insights into the rate and scale of transport across germ cells development. 

The successful candidate will be exposed to multidisciplinary aspects of the project, all of which pose fascinating opportunities for novel discoveries. The project is suitable for biochemistry, cell biology and physics students. These results will have strong implications for our cellular and molecular understanding of material exchange in germ cells and its role in fertility.