Role of glia in enteric neuronal wiring in health and Hirschsprung's disease

The Laboratory of Enteric NeuroScience (LENS) University of Leuven, Belgium is currently hiring:

PhD student in Enteric Neurophysiology

This PhD position is part of a joint PhD programme with the University of Melbourne (UoM, Australia) that includes a one year exchange with UoM.

For more information: https://melkul.research.unimelb.edu.au/
Website unit

Project

The gastrointestinal (GI) tract is a complex organ that plays essential roles in the propulsion of food and waste products, nutrient and energy uptake, as well as host defense. The enteric nervous system (ENS), a meshed network of neurons and glia, controls most of these functions. During development, progenitor cells migrate down the gut and colonize the entire intestinal tube to form the ENS. However, in 1 out of 5000 live births, these progenitors do not reach the terminal end, causing the debilitating Hirschsprung’s disease, a condition in which innervation is absent from short or longer segments of large intestine. The underlying reasons are still incompletely understood. Apart from this severe disorder, also subtler ENS defects can cause gut malfunction and discomfort. This is not surprising, as progenitors have the daunting task to travel long distances and bridge important junctions (esophagus to stomach, pylorus to the duodenum or distal ileum to colon). During their migration in the developing intestine they need to proliferate and a the correct time differentiate in neurons and glia to form a functional ENS. 

We will investigate what role glial cells play to establish long-distance connections in the ENS, we will do so using animal models as well as biopsies and resection specimen from Hirschsprung’s patients. Apart from the role of glial cells we will also address the extracellular matrix, specifically the deposited collagen which we will visualize using second harmonic imaging. One year of this PhD work will be performed in the University of Melbourne (Dr. L Stamp & Dr. M. Hao). In their lab the candidate will learn the technology to transplant induced pluripotent stem cell (iPSC) derived precursors, which will be used to investigate how cellular or extracellular matrix environment affects hosting of these cells.

Optical microscopy is one of the major techniques used in the lab. Imaging techniques have the important advantage that activity in entire cellular networks can be visualized simultaneously. With the advent of genetically encoded optical tools, a number of older microscopy techniques have regained importance as the contrast does not have to be generated by the optical approach but arises from the expression system itself. In combination with advanced (e.g. 2-photon) microscopy, it is possible to leave tissues intact and study cellular activity in situ, even at high spatiotemporal resolution. 

Key papers by LENS related to this subject: 

doi:10.1152/ajpgi.00264.2019

doi:10.7554/eLife.42914

doi:10.1002/glia.23596

doi:10.1126/science.aam7511

doi: 10.1038/nrgastro.2017.151

Profile

Profile and requirements:

• You received basic or advanced training in (neuro)physiology, neurosciences or biotechnology, and have a keen interest in technological approaches
• You are a strong team player and motivated to become part of a multidisciplinary research group.
• You communicate well in English and are able to writing a scientific text in English
• You are passionate about how neurons and cellular systems interact to control organ function.
• You are interested to understand and help solve the debilitating Hirschsprung's disease
• Experience with microscopic or electrophysiology techniques is an asset
• You are willing to move to and work in Melbourne, Australia for one year as part of the KUL-UoM exchange programme

PhD:

• You hold a master’s degree in optics/physics/technology or in the domain of life sciences (biotechnology, biology, biochemistry; bio-engineering (bio)medical sciences).
• You have a good understanding of (neuro)biology
• You have a keen interest in (optical) microscopy
• You have a critical scientific and quantitative attitude.

Offer

We offer:

• A position as a full-time (100%) PhD researcher on an annual contract basis with the possibility of renewal (max. 4 years).
• A dynamic research environment with access to multiple advanced imaging systems (confocal, multiphoton, intravital, super-resolution) set in a vast neuroscience community.
• A team with experience in GI physiology, cell culture, stem cell work, optical activity measurements and manipulation.
• Salary scales: a PhD stipend according to the university regulations is available.
• Starting date: ~december 2023 (or earlier)

LENS:  https://gbiomed.kuleuven.be/english/research/50000625/50000628/site/lens.htm

Living in Leuven: http://www.kuleuven.be/english/living

More information about the programme:   https://melkul.research.unimelb.edu.au/

KU Leuven promoters: profs. P. Vanden Berghe and M. Miserez

UoM promoters: Drs. L. Stamp and M. Hao

Interested?

For more information please contact Prof. dr. Pieter Vanden Berghe, mail: pieter.vandenberghe@kuleuven.be.
KU Leuven seeks to foster an environment where all talents can flourish, regardless of gender, age, cultural background, nationality or impairments. If you have any questions relating to accessibility or support, please contact us at diversiteit.HR@kuleuven.be.