PhD position in Molecular and Computational Neurogenomics

Antwerp VIB-UAntwerp Center for Molecular Neurology

23 May 2024

Antwerp

VIB-UAntwerp Center for Molecular Neurology

Albena Jordanova Lab, Valeriya Malysheva Lab

PhD

1

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.

Charcot-Marie-Tooth 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 aminoacyl-tRNA 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 tyrosyl-tRNA 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 dying-back 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 in-house as well as the available public data suggest mechanisms involving genetic, epigenetic and chromatin organisation factors governing the cell-type specific response to ARS mutations. Therefore, an integrative genome-wide cis-regulatory 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 cis-regulatory mechanisms underlying this disease and reveal the mechanisms underlying the strong cell-type specific effect of the CMT-causing YARS mutations. For this we will generate high-resolution 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 patient-derived iPSCs and integrate these data into the cis-regulatory networks. Following cis-GRN network reconstruction and formal graph analysis, we will identified key regulatory factors governing cell-type specific reponse to CMT-causing 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 VIB-UAntwerp 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, cutting-edge microscopy, structural biology, technology development, and bioinformatics.

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 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 state-of-the-art research and top-notch 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 patient-derived cell-type specific samples, state-of-the-art 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 state-of-the-art infrastructure and core 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 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: https://jobs.vib.be/apply/82849

Don’t 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 [email protected], [email protected] or [email protected]

VIB values diversity - in backgrounds and in experiences. The institute needs people from all backgrounds and ways of life to help build a thriving scientific environment. VIB is therefore looking for candidates who are not only strong in their own aptitudes but care deeply about supporting each other's growth. VIB's collaborators are people with different strengths, experiences and backgrounds, who share a passion for science that generates impact in science and in society. Diversity not only includes race and gender identity, but also nationality, age, disability status, sexual orientation, religion and many other parts of one’s identity. All of VIB’s employees’ points of view are key to its success, and inclusion is everyone's responsibility.