Postdoctoral Position in the Computational Neurobiology Lab

h3Postdoctoral Position in the Computational Neurobiology Lab /h3pVIBbrAntwerp, Belgium /ph3Project description /h3pIn the Computational Neurobiology lab, we study causal mechanisms underlying normal and aberrant cellular decision-making in the human brain in health and neurodegenerative diseases. More specifically, we investigate the role of spatial chromatin organization in cell fate acquisition and maintenance, using a variety of targeted and genome-wide profiling technologies and develop statistical and machine learning approaches for multimodal data integration and cis-regulatory network reconstruction. /ppWe are looking for a talented and highly motivated postdoctoral scientist to work on a project at the intersection of genetics, systems biology and computational biology to study the regulatory mechanisms underlying cell-type specific switching of alternative gene isoform in different types of dementia, generously supported by the Alzheimer's Association. /ppThe human brain shows some of the widest isoform diversity of any organ and has therefore been an important model for studying alternative splicing. Intriguingly, recent data showed widespread changes in isoform usage, specifically in usage of alternative transcription start site (ATSS) and alternative transcription termination site (ATTS) of causal disease genes, in Alzheimer's disease (AD), Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). This brings to the forefront the significance of ATTS/ATTS choice across neurodegenerative diseases and the need for comprehensive holistic research into the mechanisms regulating it, as currently the knowledge of these mechanisms is severely lacking. Most recently, large-scale changes in 3D chromatin organization and epigenetic factors have been shown to affect or correlate with alternative splicing/exon usage. Yet, a systematic study of the precise mechanisms governing ATSS/ATTS choice, on a genome-wide scale at high-resolution, and of the role of the combined action of chromatin organization and epigenetic factors in these mechanisms has not been conducted until now. The proposed project is aiming to bridge this gap via (i) building isoform-specific regulatory atlas for the human brain in health and disease, (ii) identifying causal regulatory elements and transcription factors responsible for determining ATSS and ATTS choice in disease and (iii) identifying putative causal disease isoforms with a genetic underpinning in dementia. /ph3Your profile /h3ulliEither a fully computational background (PhD in computational biology, systems biology, bioinformatics or related disciplines), or a hybrid background with a strong computational experience (PhD in molecular biology, biomedical sciences, functional genomics or related disciplines) /lilisolid knowledge of and experience in single-cell data analysis and multimodal data integration /lilisolid knowledge of and experience in reconstruction and analysis gene regulatory mechanisms /lilisolid knowledge of 3D chromatin organisation principles /liliintermediate/advanced programming skills in R and/or Python /liliexcellent communication and writing skills in English /lilistrong academic record /li /ulh3Additional beneficial skills /h3ulliexperience with analysis of 3D chromatin organization data /liliexperience with analysis of proteomics data /li /ul