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Asymmetric cell division as mechanism for generating cell diversity

Primary Supervisor: Dr Andre Pires da Silva, School of Life Sciences

Secondary supervisor: Dr Ioannis Nezis

PhD project title: Asymmetric cell division as mechanism for generating cell diversity

University of Registration: University of Warwick

During embryonic development, a single fertilised egg ultimately generates every cell of an organism. To generate diverse types of cells, some cell divisions occur asymmetrically, resulting in daughter cells inheriting different proteins and organelles. The aim of this project is to identify the genetic factors that influence asymmetric cell divisions. We discovered a mechanism for asymmetric division based on a signal from the sex chromosome. Here we will genetically identify the specific molecular factors that could mediate this new mechanism. This study will also investigate novel interactions between the X chromosome and key organelles required for cellular energy (mitochondria).

This project uses a nematode system to uncover the mechanisms controlling asymmetric cell division. It will involve the use of use state-of-the-art genome engineering techniques, microscopy and bioinformatics tools to follow molecules in living organisms and mapping genetic traits.

Note: Given the limited access to the laboratory due to the coronavirus, there is flexibility in this project to have a large bioinformatics component.

References:

  1. Shlyakhtina, Y., Moran, K.L., and Portal, M.M. (2019). Asymmetric Inheritance of Cell Fate Determinants: Focus on RNA. Noncoding RNA 5, 38.
  2. Winter, E.S., Schwarz, A., Fabig, G., Feldman, J.L., Pires-daSilva, A., Muller-Reichert, T., Sadler, P.L., and Shakes, D.C. (2017). Cytoskeletal variations in an asymmetric cell division support diversity in nematode sperm size and sex ratios. Development 144, 3253-3263.

BBSRC Strategic Research Priority: Understanding the Rules of Life: stem cells

Techniques that will be undertaken during the project:

  • Gene editing tools to generated mutant nematodes (e.g., CRISPR/Cas9)
  • Generation of transgenic nematodes (e.g., tagging of specific proteins with fluorescent markers)
  • Microscopy (e.g., time lapse videos, confocal microscopy)
  • Bioinformatics (e.g., writing scripts in Unix, R and Python)
  • Statistics (R, Python)

Contact: Dr Andre Pires da Silva, University of Warwick