Our research programme is focused on cracking the molecular code of RNA modifications and RNA regulation, as well as their connections to ageing and age-related diseases! Our team of interdisciplinary scientists is committed to uncovering the fundamental biological processes that control RNA regulation and how perturbations in these processes contribute to ageing and disease.
We know that gene regulation at the RNA level plays an important role in virtually all cellular functions and is associated with numerous human diseases, including neurodegeneration and cancer, which often accompany ageing. By understanding the molecular mechanisms that control RNA regulation and RNA quality control, we hope to shed light on the underlying causes of these age-related diseases.
Our approach is rooted in functional genomics and we have developed several high-throughput approaches to achieve our goals, including iCLIP for protein-RNA interaction mapping, in vitro iCLIP to map the binding of recombinant proteins to complex mixtures of RNAs, and miCLIP2 for detecting m6A RNA modifications. In addition, we use massively parallel reporter assays to decode regulatory elements in RNA sequences.
Over the years, we have achieved several significant milestones:
- We have found that RNA regulation is extensively modulated by interactions between different RNA-binding proteins inside cells (Sutandy et al. 2018; Kang et al 2020)
- We discovered that m6A RNA modifications mediate X-to-autosome dosage compensation in mammals (Rücklé et al 2023)
- We generated the first map of all RNA regulatory elements that control a specific splicing decision and identified splicing regulators that may contribute to CART-19 therapy resistance in B-ALL leukaemia (Braun et al 2018, Cortes-Lopez et al 2022)
- We found that the RNA binding protein Makorin acts as a sensor for faulty RNAs (Hildebrandt et al. 2019)
Currently, we focus on (1) decoding the mechanisms of splicing regulation in disease and ageing, (2) dissecting the roles of m6A RNA modifications in gene expression and dosage compensation and (3) investigating mechanisms of RNA quality control. By achieving these goals, we hope to contribute significantly to decoding the molecular principles that govern RNA regulation in human physiology and age-related diseases. Ultimately, we hope that our work will help guide the development of specific treatments.