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
We offer
As part of the VIB-UAntwerp Center for Molecular Neurology and VIB, the applicant will benefit from an established network of national and international collaborations and access to centralized facilities with expertise in bioinformatics, functional genomics and neuroimmunology. Furthermore, as part of the recently established VIB Center for AI and Computational Biology, the host lab contributes to and benefits from the strong computational and machine learning community at VIB. The successful applicant will therefore benefit from and play an active role in the life of both centres.
VIB provides a highly interactive environment and ample training opportunities for its researchers. In addition, the VIB-UAntwerp Center for Molecular Neurology is located in the city of Antwerp, the capital of Flanders, offering a culturally and historically rich, and ethnically diverse environment.
The VIB-UAntwerp Center for Molecular Neurology has 8 PIs and hosts internationally recognized leaders in the field of Neurogenetics and Neuroinflammation. Current research groups address a broad set of questions related to neurodegenerative diseases of the central and peripheral nervous system, emphasizing understanding the genetic aetiology and developing diagnostics and treatment methods for these diseases. Approaches range from human genetics, genomics, protein biochemistry and neuronal and glial cell biology to integrative systems and computational biology. Models include yeast, fly, mouse, human pluripotent human cell systems and organoids. Research groups have access to state-of-the-art research and top-notch support core facilities and attract talented international scientists worldwide.
- Financial support for one year with a formal evaluation at the end of that year. Since we are aiming for a long-term collaboration, there will be the opportunity to extend the contract following a positive evaluation.
- The applicant will be expected to actively seek independent funding and will be fully assisted in applying for personal fellowships, such as FWO, MSCA and HFSP.
- Access to state-of-the-art infrastructure and core experimental and computational facilities in a vibrant, world-class research environment operating at an international level
- Dedicated training programs available through VIB and UAntwerp to broaden your expertise and enhance your skill set
- A stimulating international research environment
- A strong and dynamic network of international collaborators
Starting date: February 2025 or as soon as possible after that.
How to apply?
You can apply for this job through the online VIB job application platform Include the following document(s):
- a CV, detailing set of mastered wet and dry lab skills and publications (2 pages max)
- a letter of motivation describing your relevant research experience and competitive profile.You have to clearly and concisely explain why you want to work on this particular project and how it fits into your career trajectory (1-1.5 pages max)
- contact details of two referees
For more information: please contact [email protected] or [email protected] https://malyshevalab.sites.vib... https://uantwerpen.vib.be
