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The impact of gut microbiome and diet interplay on neurodegeneration

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

"Neurodegenerative disorders such as Parkinson’s, Alzheimer’s or Huntington’s disease represent major health risks and economic burden for the society. Few causative genetic risks for age-associated neurodegenerative disorders have been identified, however, the role of environmental factors and gene-environment interactions responsible for disease development in most cases is still unknown. Humans, likewise many animals, host a range of microorganisms in their gut, called the gut microbiome, which influences the host’s metabolism and biological processes having both local and systemic effects. Imbalanced gut microbiome has been linked to many pathological conditions in humans, including neurodegeneration, metabolic disorders, and it can actively influence the efficiency of disease treatments.

Studying the mechanistic link between gut microbiota and disease progression in humans is difficult due to heterogeneity of human and microbial genomes involved. Hence, the use of simple organisms such as C. elegans is gaining growing interest in gut microbiome research providing easy, fast and genetically homogenous model for microbiome-host interaction that can be subjected to large-scale and high-throughput genetic screening. Recent research showed that altered metabolism of the feeding bacteria has profound effects on the lifespan of C. elegans and demonstrated the great potential of C. elegans as a model of gut microbiome-regulated ageing and disease progression and its clinical relevance to human studies.

This project aims to examine the largely unexplored field of gut microbiome-host interaction, and its impact on the host metabolism and neurodegeneration. Diet induced changes in gut microbiota has been previously implicated in dysregulation of food intake and body weight control (PMID: 31242699) leading to undesired effects on host health (obesity and associated diseases). However, the molecular mechanism linking gut microbiome alterations to host metabolic changes and subsequent adverse effects on the host neuronal system are still largely unknown. We have previously screened over 400 deletion mutant E. coli strains (using them as genetically homogenous diet) for modifying the mitochondrial homeostasis of the worms and identified multiple bacteria mutants that affects mitochondrial stress response, suggesting prominent effect of the bacteria (microbiome) on the worm metabolism. We also use C. elegans obesity models to investigate the impact of metabolic disorders on human diseases. This project will utilize our existing C. elegans genetic models of Parkinson’s disease to investigate cellular pathways and tissue specific signalling mechanisms that are influenced by the gut microbiome and various obesogenic diets. The project aims to shed light on how gut microbiome exerts its effect on human neurodegenerative diseases, with special focus on Parkinson’s disease. Student involved in this project will use genetic, molecular, cell biology and behavioural techniques in their study and will be part of a vibrant collaborative group at the University of Reading, with an opportunity to get training in teaching pedagogy."

Funding Notes

Applicants should hold or expect to gain a minimum of a 2:1 Bachelor Degree or equivalent in a Biology related subject. Experience with C. elegans or with cell culture would be advantageous, but not a pre-requisite.

References

References

Tawo, R., W. Pokrzywa, E. Kevei, M. E. Akyuz, V. Balaji, S. Adrian, J. Hohfeld and T. Hoppe. ""The Ubiquitin Ligase Chip Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover."" Cell 169, no. 3 (2017): 470-482 e13.
Franz, A., E. Kevei and T. Hoppe. ""Double-Edged Alliance: Mitochondrial Surveillance by the Ups and Autophagy."" Curr Opin Cell Biol 37, (2015): 18-27.

Kevei, E. and T. Hoppe. ""Ubiquitin Sets the Timer: Impacts on Aging and Longevity."" Nat Struct Mol Biol 21, no. 4 (2014): 290-2.
Hirschberg, S., Gisevius, B., Duscha, A. & Haghikia, A. (2019) Implications of Diet and The Gut Microbiome in Neuroinflammatory and Neurodegenerative Diseases, International journal of molecular sciences. 20.
Heintz, C. & Mair, W. (2014) You Are What You Host: Microbiome Modulation of the Aging Process, Cell. 156, 408-411."

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