PhD position in Molecular and Computational Neurogenomics
PhD position in Molecular and Computational Neurogenomics
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Job Description
Project description
We are a highly motivated international team of researchers at the Molecular Neurogenomics group (Jordanova Lab) and the Computational Neurobiology group (Malysheva Lab) at the VIB CMN. We are excited to announce a call for a joint PhD student in our labs to work on a challenging project at the interface of neurodegeneration genomics computational and systems biology.
CharcotMarieTooth disease (CMT) represents the most common genetic disorder of the peripheral nervous system. Patients experience progressive distal muscle weakness and wasting sensory loss and skeletal deformities ultimately leaving them severely disabled. This lifelong disorder is currently incurable. The largest protein family implicated in the etiology of CMT are aminoacyltRNA synthetases (ARS). Ubiquitous and essential enzymes ARS catalyse a critical step in protein biosynthesis by charging tRNA with their cognate amino acid. Jordanova Lab reported that dominant mutations in the tyrosyltRNA synthetase (YARS) cause a clinical variant of CMT and so far six additional cytoplasmic ARS have been implicated in the same pathology.
The overarching goal of this proposal is to understand why and how dysregulation of omnipresent and constantly expressed ARS proteins leads to dyingback neurodegeneration and affects specifically the peripheral neurons (PNs). This neuronal population contains the most polarized cells in our body and their sophisticated morphology and function render them highly susceptible to degeneration. The preliminary data generated inhouse as well as the available public data suggest mechanisms involving genetic epigenetic and chromatin organisation factors governing the celltype specific response to ARS mutations. Therefore an integrative genomewide cisregulatory network analysis approaches developed and employed in the Malysheva Lab are required to reveal these mechanisms.
With the proposed project we aim to bridge this gap in our knowledge of cisregulatory mechanisms underlying this disease and reveal the mechanisms underlying the strong celltype specific effect of the CMTcausing YARS mutations. For this we will generate highresolution spatial chromatin organisation chromatin accessibility and gene expression data for all major cell types forming the peripheral nerve environment (as well as controls) generated from the patientderived iPSCs and integrate these data into the cisregulatory networks. Following cisGRN network reconstruction and formal graph analysis we will identified key regulatory factors governing celltype specific reponse to CMTcausing mutations. Finally we will validate the identified key (epi)genetic molecular and eplore their therapeutic potential in in vitro and in vivo disease models.
Profile
The candidate should:
- have an MSc in Systems Biology Molecular Biology Natural Sciences or related disciplines
- be very motivated and enthusiastic to learn and expand both computational and experimental skill sets
- have an analytical mindset
- be able to summarize data extracted from the literature and clearly shape research objectives
- be able to efficiently communicate with experimental and computational scientists
- have excellent communication and writing skills in English
Required skills
- confident in basic molecular biology techniques such as cell cultures basic genomics data generation
- knowledge of (theory behind) gene regulatory mechanisms and multimodal data integration
- basic/intermediate programming skills in R and/or Python
- Ability to adapt to the research environments while being full members of two labs
Desirable skills
- statistical analysis
- basic processing of NGS data
- experience with iPSC and/or cell culturing
- knowledge of and some experience with genetic perturbation assays such as CRISPR
We offer
As part of the VIBUAntwerp Center for Molecular Neurology and VIB the applicant will benefit from established collaborations and access to centralized facilities with expertise in genomics functional genomics and cell biology proteomics cuttingedge microscopy structural biology technology development and bioinformatics.
VIB provides a highly interactive environment and ample training opportunities for its researchers. In addition the VIBUAntwerp 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 VIBUAntwerp Center for Molecular Neurology has 7 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 with an emphasis on understanding the genetic etiology 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 and pluripotent human cell systems. Research groups have access to stateoftheart research and topnotch support core facilities and attract talented international scientists from across the world.
- By the end of the PhD the successful candidate will graduate with a highly competitive set of experimental and computational skills such as generation and characterization of patientderived celltype specific samples stateoftheart molecular biology techniques multimodal data generation and integration gene regulatory network reconstruction and wide range of machine learning approaches
- The host labs will provide financial support for the whole length of the PhD.
- The applicant will be expected to actively seek independent funding and will be fully assisted in applying for personal fellowships such as FWO BOF DOCPRO and BIF.
- Access to stateoftheart infrastructure and core facilities in a vibrant worldclass research environment operating at an international level
- Dedicated training programs available through VIB and UAntwerp to broaden your expertise and enhance your skillset
- A stimulating and international research environment
- A strong and dynamic network of international collaborators
Starting date: as soon as possible open to negotiation
How to apply
You can apply for this job through the online VIB job application platform:
Dont forget to include the following document(s):
- a detailed CV highlighting mastered experimental and computational skills and publications if any
- a letter of motivation concisely describing 1) your relevant research experience and competitive advantages 2) your interest in the experimental and comptutational aspects of the proposed project (max 2 pages)
- contact details of two referees
For more information: please contact or
Employment Type
Full Time
