Comparative effects of alcohol and GABA mimetics on the brain-gut-microbiota (BGM) function

Applications are invited for a fully-funded four-year PhD to commence in October 2023. 

The studentship is jointly funded by the South Coast Biosciences Doctoral Training Partnership (SoCoBio DTP) as well as an industrial partner, GABA Labs. SoCoBio is a Biotechnology and Biological Sciences Research Council (BBSRC) funded DTP offering a broad, 4-year research training programme which provides students with the skills they need to develop into future bioscience leaders in academia or in industry.

The PhD will be based in the Faculty of Science and Health at the University of Portsmouth and will include interactions with scientists from GABA Labs, as well as the wider SoCoBio training network at our partner institutions (Southampton, Sussex, Kent). The direct supervisors will be Professor Jerome Swinny and Dr Murphy Wan of the University of Portsmouth, and Dr Delia Belelli from GABA Labs. 

Successful applicants will receive a bursary to cover tuition fees at the UK rate for four years, a stipend in line with the UKRI rate (£17,668 for 2022/23), and funding to cover project costs/consumables. 

The work on this project will investigate:

●      How the neurotransmitter GABA integrates the functions of the brain, gastrointestinal (GI) tract, and resident GI bacteria or microbiome, to mediate homeostasis throughout the nervous system and the body. 

●        How botanically derived compounds impact on the functioning of these GABA systems within this brain-gut-microbiome axis.

●        How the effects of these botanically-derived compounds compare with the effects of alcohol on the brain-gut-microbiome axis.

Project description

The gut and its resident bacteria contribute to a variety of brain functions and disorders. The chemicals mediating communication within the brain-gut-microbiota (BGM) axis include both microbiota metabolites and classical neurotransmitters, notably GABA. This is important because alcohol is one of the most widely consumed GABA mimetic agents, both recreationally throughout the populace or compulsively by addicts with a significant burden to individuals and society. Accumulating evidence implicate alcohol-induced microbiota’s alterations in reward-seeking behaviour and increased risk of developing psychopathology. Therefore, understanding how various GABAergic networks are integrated throughout the BGM, and influenced by alcohol, could help identifying safer alternatives. 

The commercial partner for this project, GABALabs, has identified novel, botanical, GABA mimetic agents that hold such promise. However, to develop these compounds as safe beverages for human consumption, it is essential to determine their effects on GABA-receptor function and mammalian BGM homeostasis. This is because different segments of the BGM axis appear to employ divergent GABA receptors, thus likely resulting in varied local GABA actions and a myriad of physiological effects. Therefore, the aims of this project are to characterise the various GABA-receptor pathways within and between segments of the BGM axis, and then determine the impact of these compounds upon GABAergic signalling and BGM homeostasis in comparison to alcohol.

A multidisciplinary approach and supervisory expertise will be adopted. This will include RNASeq transcriptomics to characterise the comparative GABA molecular machinery within the different BGM cellular networks, proteomic to determine protein expression, medicinal chemistry to derive GABA-mimetic compounds from botanicals, electrophysiology to functionally and pharmacologically assess GABA receptor modulating botanicals, and a suite of intestinal, microbiome, neural and behavioural assays to determine their overall effects on BGM homeostasis. 

The ideal candidate should be keen to adopt a cross-disciplinary approach to addressing complex biological questions and delivering impact from research.

General admissions criteria

You'll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in an appropriate subject. In exceptional cases, we may consider equivalent professional experience and/or qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

Specific candidate requirements

You should have a strong academic and technical background in biology, biomedical sciences, neuroscience, pharmacology, biophysics or microbiology. You should also have a strong interest in adopting a multidisciplinary approach to the research questions, including using Gene expression analyses (RNASeq; qPCR, in situ hybridisation such as RNAScope),  Protein expression and localisation analyses (immunohistochemistry and confocal microscopy; Flow cytometry), Electrophysiology (Biophysical and pharmacological properties of botanical compounds using two electrode voltage clamp recordings of various GABA receptor subtypes in heterologous expression systems such as Xenopus oocyte and various functional assays (Gastrointestinal motility;  Bacterial-epithelial cell interaction assays). Full training will be provided in all techniques.

These techniques will be complemented with an in-depth industry training in botanical/medicinal chemistry (Extraction, purification and quality assessment of GABA mimetic compounds from botanicals) with investigators from the industry partner GABALabs. In addition, they will gain training in relevant non-science areas such as commercial scale up, product development, marketing and communication.

How to Apply

You are welcome to contact Professor Jerome Swinny (jerome.swinny@port.ac.uk) to discuss your interest before you apply, quoting the project code.

When you are ready to apply, you must use the SoCoBio application portal. Applications sent directly to the supervisors will not be considered.