Off-Road grant for Yang Li

Postdoc Yang Li of the Dept of Genetics has been awarded an Off-Road grant (€125k) by ZonMw for her project proposal that aims to identify cell-type-specific genetic effects on gene expression in biopsies of tissues that are relevant to disease. This is one of nine grants awarded for "high-risk -- high-gain" proposals that are at a start-up stage and it will finance 18 months of her research work.

The purpose of ZonMw's Off-Road programme is to challenge talented, early career, medical/biomedical, health or technical researchers to make new insights and achieve breakthroughs in medical and/or health research. The projects are meant to be out-of-the-box and thus risky, with no prior knowledge or pilot data required. ZonMw therefore accepts that a fair number of these projects will not lead to the results aimed for.

The grants have also been awarded to projects ranging from looking at defence mechanisms to destroy cancer cells to finding individual factors that can predict the course of Parkinson’s disease.

Summary
Every cell counts: single cell RNA-sequencing of biopsies to uncover disease and cell-specific expression effects

Through genome-wide association studies, hundreds of single nucleotide polymorphisms have been found to be associated with autoimmune diseases. Although some of these have been shown to be associated with variation in gene expression, displaying a so-called expression quantitative trait locus (eQTL) effect, for most of the SNPs an eQTL effect was not observed. The reason for this is that eQTL effects are highly cell-type-specific and not all the disease-associated cell types have been discovered. In this project I propose to: (1) identify cell-type-specific expression profiles for all the cells present in a patient-derived biopsy, (2) reveal all the potentially rare cell types involved in this disease, and (3) use these profiles to develop a computational cellular deconvolution strategy that will allow us to determine cell-type-specific eQTL effects, starting with RNA-seq data obtained from a whole biopsy.

While I will be focusing on intestinal biopsies from celiac disease patients as a model, my strategy will be applicable to every complex tissue sample involved in any disease with a genetic component.

Contact Yang Li - email