Postdoctoral Position in the Lab of Computational Neurobiology

Postdoctoral Position in the Lab of Computational Neurobiology

VIB

Antwerp, Belgium

Project description

The Computational Neurobiology lab studies causal mechanisms underlying normal and aberrant cellular decision-making in the human brain in health and neurodegenerative diseases. 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.

We are looking for a talented and highly motivated scientist for a postdoctoral position in our lab to work on a project at the intersection 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.

The 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 studies 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). These observations 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, there has never been a systematic study of the precise mechanisms governing ATSS/ATTS choice, on a genome-wide scale at high-resolution, nor of the role of the combined action of chromatin organization and epigenetic factors in these mechanisms. The proposed project is aiming to bridge this gap, (i) build isoform-specific regulatory atlas for the human brain in health and disease, (ii) identify causal regulatory elements and transcription factors responsible for determining ATSS and ATTS choice in disease and (ii) identify putative causal disease isoforms with a genetic underpinning in dementia.

Required skills

The candidate should:

  • have a PhD in biomedical sciences, molecular biology, cellular biology, systems biology orrelated disciplines
  • possess advanced molecular and cellular biology skills, including approaches for generation ofomics data, FACS/FANS and CRISPR-mediated perturbation approaches
  • have solid knowledge of and experience in single-cell data analysis and multimodal dataintegration
  • have strong knowledge of gene regulatory mechanisms
  • have basic/intermediate programming skills in R and/or Python
  • have excellent communication and writing skills in English
  • have strong academic record

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