The 2019 PhD scholarship round is currently open. Please contact us if you are interested in any of the following projects.
Optimal guide design for base editors
The main applications of CRISPR for gene editing rely on a guide RNA (gRNA) engineered to bind at a specific location of interest in the genome, and on Cas9 to 'follow' this guide and make a cut at that position. A more recent approach is to use 'base editors' that combine enzymes modifying DNA with inactive Cas9 variants. This allows base changes without cut, DNA repair mechanism or donor template. This has a huge potential, but the performance of base editors is still incompletely characterised.
In this project, you will develop a computational method to design optimal gRNAs for base editors, and validate these results in the context of human induced pluripotent stem cells (in partnership with local collaborators). You will investigate the efficiency of the guide, as well as characterise the off-target effects and discover determinants that influence the targeting specificity of gRNA. By doing so, the objective is to develop an optimised gRNA selection and design platform that can be used to accelerate human stem cell research
Quantitative analysis of high-resolution 3D brain images
Tissue clearing allows the imaging of entire organs at a single-cell resolution. It is becoming a very important in neurosciences. One of the main challenge currently lies with the data being produced: there is more to do with 3D whole-organ images than a simple qualitative description. However, analysis is not trivial.
In this project, you develop methods to accurately detect and extract the signal from cells of interest (e.g. Arc-dVenus expression, or cells labelled with a specific antibody), and quantitatively analyse this signal across multiple brains. This will involve registering brains to a reference atlas, and creating new representations of the results (e.g. interactive visualisation).
You can read more about our tissue-clearing work here.