Probing Death Decisions from Morphogen Gradient Fields

About the Project

Morphogen gradient scaling is one of the hottest fields in developmental biology at the moment. Scaling is fundamental, explaining how the machinery that controls pattern formation in development (the morphogens) can adapt, so that organs of different sizes show morphological structures which are proportioned. The same developmental machinery can build the leg of a mouse, an elephant or a tumour.

Living systems compete with each other on the basis of available resources, mating or space. It's not surprising that, within the living individual, the basic functional units of life - the cells - share these competitive attributes1. Cells compete for survival factors, space and also compare fitness traits to win the race of subsistence1-3. Cell Competition was found in Drosophila, where the so-called unfit cells were eliminated from the organ when confronted to the so-called fit cells4. Nowadays, we know that there are several mutations triggering these “battles”, where the 'unfit cells' are eliminated from the tissue in the presence of the 'fit' ones1, 3-19.

In our recent work (Merino et al. 2022, Nature Cell Biology and Merino et al. 2022, Trends in Cell Biology) we found that Cell Competition is reminiscent of what happens in wildtype during Dpp morphogen gradient scaling. The difference between 'unfit' and 'fit' cells has been shown to be able to be encoded by different levels of Dpp signalling, and that this is reminiscent of the spatial decay of the gradient15, 16, 20-25. If the gradient is not properly scaled (i.e. if the gradient is shorter than the tissue), then a 'death program' is triggered. Indeed, this is a novel phenomenon calledDeath-mediated scaling3, 16, 19.

Using state-of-the-art techniques in biophysics (FRAP, FLIM, nanobody internalisation), molecular genetics and biochemistry, this project aims to unveil the mechanistic bases of the 'Death-mediated scaling' machinery during morphogen scaling and organ growth.

Lab & Institute culture

You will work in the lab, under the close supervision of the principal investigator (PI). I maintain an open door policy and aim to lead by example. The successful applicant will meet the PI at least once per week to brainstorm and discuss new research avenues.

Every member of the lab presents in the weekly lab meeting, and paper discussion activities (e.g. journal clubs) are organised to discuss the latest published research. You will have the opportunity to present your work in internal seminars run by our institution. These seminars are a valuable feedback opportunity, allowing you to profit from the exciting multidisciplinary scientific environment of the Institute of Systems, Molecular and Integrative Biology.

As part of your PhD training, you will also support at least one national conference per year, as well as one international conference within the duration of the project.

Our EDI policy

Life and research experience have taught me to create inclusive and diverse bonds in my scientific interactions. I believe this is a path to building more enriching, deep and successful research. In my career, I have promoted equity and diversity at different academic levels and I have also completed my EDI training at the University of Liverpool. As a Research Group Leader in the lab and in my teaching roles, I aim to continue to promote and expand these values (in line with those of the University). I am overall committed to the University mission of achieving research and academic excellence in an inclusive manner.

This is your place

Given the nature of this project and the excellent scientific environment available, you will use cutting-edge imaging technology and novel cell biology assays. This offers researchers the opportunity to develop original experimental skills and establish a scientific network from an early stage. Altogether, this training and support will greatly contribute to asuccessful PhD defence as well as todeveloping key and unique scientific skills.

Applications

We encourage you to apply for this position as soon as possible.

Review of applications will begin immediately and continue until the position is filled. Please note that the deadline may therefore be subject to change.