Understanding the links between neurodegenerative diseases and the human microbiota

Dementia is characterised as a syndrome associated with an ongoing decline of brain functioning, with symptoms including memory loss, a decline in mental sharpness, quickness and understanding, and difficulties in carrying out daily tasks. The science is straightforward but devastating: the human brain is composed of billions of connected nerve cells – conditions like Alzheimer’s block those connections with protein aggregates called amyloid plaques. Unable to communicate, the nerve cells gradually degenerate and die, slowly diminishing the sufferer’s brain tissue.

Whilst contemporary treatments focus on relieving the worst symptoms via a combination of drugs, palliative care, and bespoke counselling services, the catastrophic damage caused by Alzheimer’s disease is irreversible and the associated neural degeneration cannot be halted nor prevented.

By harnessing knowledge spanning a range of fields, this PhD studentship will form part of a large interdisciplinary project, pursuing an innovative approach to treatment of Alzheimer’s disease. This PhD studentship will study the potential link between the microbiota and Alzheimer’s disease. The gut microbiota forms biofilm structures where unidentified molecules are excreted and hypothesised to interact with amyloid precurson protein and/or other proteins such as the β, γ-secretases or amyloid beta monomers/oligomers promoting aggregation-prone amyloid-beta peptides, which are centrally implicated in the pathogenesis of Alzheimer’s disease.

This PhD studentship will therefore characterise a carefully selected set of small intestinal bacterial isolates, under a variety of conditions ranging from standard planktonic growth to conditions that better mimic the small intestine via development of a small intestine model. The excretome will be characterised by mass spectrometry and analytes from this diagnostic will be screened using computational chemistry to quantify their potential binding and interaction with amyloid precurson protein and other proteins including β, γ-secretases and amyloid beta monomers/oligomers. Lead molecules from this computational study will be synthesised and applied to a newly developed blood brain barrier model to study their mode of action and determine a potential therapeutic treatment or preventative step.

The successful applicant will gain diverse training in microbiology and computational chemistry. They will also gain significant experience in working as part of a large interdisciplinary team. Studies will be supported by the School of Science and Technology at Nottingham Trent University, the 2023 Modern University of the Year (Times Higher Education). The successful applicant will have a bachelor’s degree in microbiology, or related discipline, and/or a master’s degree in a relevant subject area and a keen interest in working as part of an interdisciplinary team to address this major healthcare challenge.