PhD Studentship: Spindle orientation in the developing fly embryo: a joint mathematical-experimental approach. BBSRC SWBio DTP PhD studentship 2025 Entry

About:

The BBSRC-funded SWBio DTP involves a partnership of world-renown universities, research institutes and industry, based mainly across the South West and Wales.

This partnership has established international, national and regional scientific networks, and widely recognised research excellence and facilities.

We aim to provide you with outstanding interdisciplinary bioscience research training, underpinned by transformative technologies.

Project Description

Despite decades of research, the very earliest stages of animal development are still not well understood. Some of the most fascinating unsolved questions are related to cellular symmetry breaking. How do cells formed from the first few divisions of the fertilised egg orientate themselves? How is cell orientation influenced by the neighbouring cells? And what happens when cell orientation goes wrong?

To answer such questions, it is important to first start with relatively simple cases. For this reason, the organism of choice for this field is the fruit fly, Drosophila. Its rapid life cycle and existence of transgenic flies expressing fluorescent proteins important in cell division make it possible to see exactly how cells are orientated and to follow this in real time.

Traditionally, problems like this have been tackled with a purely experimental approach. However, much quicker progress can often be made if instead mathematical modelling is intimately combined with experiments. This is the exciting program you will follow during this PhD.

You will use a multidisciplinary approach that combines mathematical modelling, computer simulations, light sheet microscopy and image analysis. This will allow you to learn a wide range of different skills and techniques, ideal for a future career in academia or elsewhere. You are not expected to already know both mathematical modelling and wet-lab techniques; full training will be provided in both areas during the PhD.

In particular, during this project, you will:

1. Design a three-dimensional mathematical model of mitotic spindle orientation. This will be based on the famous Ising model of interacting spins from physics. These models will be simulated and analysed using MATLAB, Python and/or C++.
2. Use our brand new, state-of-the-art light sheet microscope to learn how to handle and genetically manipulate fruit flies and then obtain images of the developing Drosophila embryo.
3. Develop image analysis software to automatically extract the spindle orientation. This will then be able to inform both the mathematical modelling in part 1 and the experiments in part 2.
4. Apply the experimental approach and the mathematical model to the oriented cell divisions of the Drosophila larval testes niche.

This interplay between experiment and modelling is a key part of this project and will make for a truly exciting PhD.

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