This is a summer student position supervised by Lewis Mosby from Zena Hadjivasiliou's lab.
Introduction to the Science
The size, shape and patterning of animals are thought to be governed by the distributions of evolutionarily conserved molecules called morphogens, which activate different genes in a concentration-dependent manner. Following localised secretion at one end of a tissue, morphogens form decaying distributions through the processes of diffusion and degradation. In order for patterns to adapt as animals grow, it is vital that the characteristic length scales associated with morphogen gradients scale with the size of the animal, and also that these distributions are robust to fluctuations in morphogen production. This scaling behaviour has been found experimentally in many model systems.
About the Project
From a theoretical perspective, morphogen gradient scaling can be achieved by introducing bidirectional feedback between morphogens and other diffusing molecules. This project aims to understand whether this feedback can also ensure the robustness of morphogen distributions by studying the downstream effects of time-dependent perturbations in morphogen production. For certain feedback mechanisms, strong coupling between the concentrations of morphogens and other molecules can cause the unstable growth of concentration fluctuations. Understanding the origins of such instabilities will provide important insights into how robustness is achieved in nature. This project is a great opportunity to learn about how mathematical and physical approaches are applied to the study of biology, as well as how to use different scientific programming languages (such as C++ and Julia) and high-performance computing platforms.
We are looking for an enthusiastic student with an interest in coding and biophysical research. This project would suit a candidate studying maths, physics, computer science or a similar discipline, who is curious about biology, or a biology student interested in developing their modelling and quantitative skillset. A preliminary mathematical model and associated code will be provided, but prior experience in programming and solving differential equations would be advantageous.
1. Ben-Zvi, D. and Barkai, N. (2010)
Scaling of morphogen gradients by an expansion-repression integral feedback control.
Proceedings of the National Academy of Sciences of the United States of America 107: 6924-6929. PubMed abstract
2. Adelmann, J.A., Vetter, R. and Iber, D. (2022)
Preprint: Patterning precision under non-linear morphogen decay and molecular noise.
Available at: bioRxiv. https://doi.org/10.1101/2022.11.04.514993