Full funded PhD position available: The impact of cell division on the decoding of oscillatory protein expression during spinal cord development and regeneration

A 4-year PhD position funded by the Medical Research Council (MRC) Doctoral Training Partnership (DTP) is available at the University of Manchester, supervised by Dr. Anzy Miller, Dr. Holly Lovegrove, Dr. Veronica Biga and Dr. Karel Dorey.

We invite applications from driven and curious PhD candidates to study how oscillatory protein expression interacts with cell division to impact cell fate decisions and the timing of neural differentiation in the developing spinal cord.

What’s the project about?

The production of neurons needs to be precisely regulated so that the nervous system develops correctly. The expression of proneural genes, like Neurogenin 2 (NGN2), play important roles in driving stem/progenitor cells towards a neuronal fate.  What matters, however, is not just whether these proteins are present, but also their pattern of expression over time. For example, steady expression can have different effects compared to oscillatory expression (repeated peaks and troughs in protein levels over time). At the same time, these neural progenitor cells must also keep dividing to expand their numbers, ensuring there are enough cells to build a complete nervous system. However, what remains poorly understood is how these oscillatory expression patterns interact with the process of cell division. This project will aim to investigate that connection using human embryonic stem cell-derived neuronal progenitors. How does cell division impact on oscillatory protein expression and cell fate? Together this work will provide new mechanistic insights into how neural cells are made, which is a fundamental biological process with implications for development, regeneration and disease.

In order to investigate these questions, the student will use a CRISPR-edited stem cell line that will allow us to track both cell divisions and NGN2 oscillations in real time, in 2D cultures and 3D organoid systems. Computational approaches (including AI-models) will be used to assess and predict how cell division might influence the genetic feedback loops that generate oscillatory expression. These predictions will then be tested experimentally using genetic manipulations (via CRISPR-Cas9 genetic editing), inducible expression systems and drug treatments (using state-of-the-art microfluidic tools) during the development of neurons. Finally, we will investigate these mechanisms after the cells have been exposed to stresses/injury to assess their role in regeneration.

Interested?

Contact anzy.miller@manchester.ac.uk for details and how to apply. Please include CV and a brief statement about your interests and fit to the project.