The enteric nervous system during ageing in health and disease

1 PhD project offered in the IPP summer call 2021

This project is part of the Science of Healthy Ageing Research Programme (SHARP).

Scientific background

The gut of mammals provides the largest neuronal entity outside the brain, the so-called enteric nervous system (ENS), organized in a mesh-like structure. Despite this obvious architectural difference to the brain, significant similarities link the ENS and brain, such as the use of the same neurotransmitters and the support of neurons by glial cells in both systems.

For the central nervous system (CNS), it is well established that neurons fade away with age - especially when the ageing process is exacerbated, such as in Alzheimer’s disease. With regards to the gastrointestinal system (GS), motility, absorptive function, and immunity have all been shown to decline with age. Nevertheless, the GS exhibits considerable reserve capacity and can preserve certain functions such as intestinal secretion. While the physiology has been studied for some time, underlying changes in the nervous system of the gut, the enteric nervous system (ENS), have been largely neglected.

First results indicate a strong correlation between age-related CNS diseases and ENS aberrations and functional decline. These observations provide a strong impetus for an in-depth characterization and understanding of the underlying alterations within the ENS during ageing and in Alzheimer’s disease.

PhD project: Ageing and functional decline of the enteric nervous system in Alzheimer’s disease and senescence-accelerated mouse models (“AGENS”)

The aim of this PhD project is to decipher how the ENS changes during healthy and diseased (Alzheimer’s) ageing and how these changes affect the gut and its function. This may open up new diagnostic approaches and treatment options for Alzheimer’s disease patients.

For this purpose, a senescence-accelerated mouse model and an Alzheimer mouse model will be used. Molecular and functional analyses will be performed on tissue as well as organoid cultures derived from these and control mice at different ages. Finally, the findings from the mouse models will be translated into clinically relevant information by using human organoids derived from participants of the “AgeGain” study.

The project is highly interdisciplinary combining various research areas and techniques, including mouse models and organoid cultures, telomere und epigenetic analysis, histology and microscopy, next-generation sequencing (e.g. RNA-seq) and bioinformatics as well as various functional assays. We are therefore looking for a highly motivated PhD candidate with good communication skills, who is enthusiastic about the research topic, eager to drive the project and brings relevant wet lab experience. Familiarity with working in tissue culture is desired. The candidate’s primary affiliation will be with the Psychiatry Department but he/she will be trained and may conduct experiments in each of the participating groups. These include Peter Baumann (IMB/JGU), Kristina Endres (UMC), Sandra Schick (IMB), and Oliver Tüscher (UMC).

If you are interested in this project, please select Peter Baumann as your group preference in the IPP application platform.

Publications relevant to the project

Tseng CK, Wang HF, Schroeder MR, Baumann P (2018) The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN. Nature Commun, 9(1):5430 Link

Stoye NM, Dos Santos Guilherme M, Endres K (2020) Alzheimer's disease in the gut- Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player. FASEB J, 34(9):11883-11899 Link

Varga J, Nicolas A, Petrocelli V, Pesic M, Mahmoud A, Michels BE, Etlioglu E, Yepes D, Haupl B, Ziegler PK, Bankov K, Wild PJ, Wanninger S, Medyouf H, Farin HF, Tejpar S, Oellerich T, Ruland J, Siebel CW, Greten FR (2020) AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer. J Exp Med, 217(10):e20191515 Link

Endres K, Schäfer KH (2018) Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases. J Innate Immun, 10(3):172-180 Link

Wolf D, Tuscher O, Teipel S, Mierau A, Struder H, Drzezga A, Baier B, Binder H, Fellgiebel A; German AgeGain study group (2018) Mechanisms and modulators of cognitive training gain transfer in cognitively healthy aging: study protocol of the AgeGain study. Trials, 19:337 Link

 

Contact

Prof. Peter Baumann (If you are interested in this project, please select Peter Baumann as your group preference in the IPP application platform.)

Email

Webpage

Dr Kristina Endres

Email

Webpage

Dr Sandra Schick

Email

Webpage

 

Prof. Oliver Tüscher

Email 

Webpage