Identification and in vivo characterisation of gut-bacterium interactions involved in immunity and ageing.

As population ageing increasingly weighs on our economies, tackling ageing co-morbidities is now a priority. Previously neglected, gut host-microbe interactions have revealed critical determinants of human health and age-associated co-morbidities, including chronic infections, autoimmune diseases (Crohn’s), cancer, metabolic (diabetes mellitus, metabolic syndrome) and neurological diseases (Alzheimer’s, Parkinson’s, mood disorders) [1]. While the complexity of such interactions limits their investigation in mammals, their conservation across animals offers the possibility of studying them comprehensively in simpler model organisms, such as the roundworm Caenorhabditis elegans. This model system provides full control over microbiota composition, genetically tractable host and microbe(s) (sequenced and annotated genomes, mutant, RNAi and transgenics libraries), and allow for a wide range of fast, affordable, expedient and quantitative phenotyping assays (from life trait to pathology and behavioural analysis) [2, 3]. Gaining a comprehensive view of how the genomes of a simple animal and its gut bacteria interact (which genetic networks are engaged and how they talk to each other in health and disease) can identify new drug targets for pharmacological approaches, allow for their rapid testing in vivo, and help predict unanticipated effects. Owing to the conservation from worms to men of genetic pathways, physiological functions and gut-microbe interactions, methodologies and outcomes of such work naturally translate into human health.

You will study interactions between the roundworm Caenorhabditis elegans and opportunistic human pathogens (Gram-positive and Gram-negative) that cause infections and affect the healthspan and lifespan of the worm. You will use recently developed high-throughput assays [4] to perform RNAi screens for infection resistance. Combined to RNA sequencing, it will allow you to pinpoint genetic networks engaged in different phases of infection (from the recognition of a new microbe to host death), infection/strain-specific responses, and core worm-bacterial communication systems. Screening of bacterial mutant libraries against selected worm RNAi hits will reveal synergetic interactions between bacterial and worm genes, thus identifying interconnected host-bacterium pathways. Functional validation of these pathways in the context of worm ageing, metabolism and immunity will involve semi-quantitative pathophysiological studies [5], in aged or drug-treated animals expressing fluorescent reporters and fed fluorescent bacteria.

This multidisciplinary project will train you on widely transferable techniques in microbiology, genetics, bacterial and worm transgenesis, genomic dataset analysis, microfabrication, confocal fluorescence imaging and image analysis. Your project will be supported by brand new imaging, microfabrication, and C. elegans facilities set within the stimulating and collegial scientific environment of the Faculties of Health and Medicine (FHM) and Science and Technology (FST).

For this competitive fully funded position, we are seeking an ambitious, driven and academically accomplished student with sound laboratory experience in microbiology and/or molecular/cellular biology and/or genetics. Please contact [Email Address Removed] and [Email Address Removed] with an updated CV and cover letter to register interest.

Applications are made by completing an application for PhD Biomedical and Life Sciences October 2018 through our online application system. Closing date: midnight 28th February 2018.