Manipulation of neuroimmune responses and behaviour by infectious agents

About the Project

The project focuses on how infectious agents modify the individuals that they infect and how neuroimmune responses to infection moderate behaviour changes in warm-blooded animals and humans. Infection has been associated with behavioural changes in animals, with pathogens that reach the brain among the most prominent.

This project extends our finding that the parasite Toxoplasma (among the top 5 neglected parasitic infections in the US) modifies behaviour and neurotransmission. In this case signals sent from infected cells to neurons alter norepinephrine expression from its central site, the locus coeruleus. This signalling may apply to viral infections such as those with SARS-CoV-2 in Long-COVID with symptoms including fatigue, brain fog and impaired cognition, fitting well with our recent host genomic association with COVID severity (Nature 617:764 2023). We are studying the effects of both these pathogens on neurophysiology and neuroimmune responses. This project furthers new findings of messengers from infected cells to neurons that mediate gene expression through epigenetic modulation (Nature Sci Reports 13:6913 2023). Neurophysiological changes will be investigated as well as their impact on neuroimmunity. The signalling messengers responsible will be characterised utilising genomic approaches. The role of noradrenergic regulation of cytokines in mouse models will be examined. Correlation of phenotypes with cognitive behaviour changes will be measured. The signalling mechanisms and epigenetic alterations in gene expression underlying behaviours will be delineated. These will entail mechanisms such as transcriptional gene silencing and RNA silencing.

You will learn and utilise a wide variety of in vivo, cell and molecular techniques including rodent behaviour testing, engineered mouse CRISPR-Cas gene knockout lines, intracranial cannula implants, recombinant viral vector neuronal gene delivery, cell and parasite cultivation, human and animal sera work, biochemical fractionation, HPLC-electrochemical detection, ELISA, confocal and fluorescence microscopy, quantitative reverse transcriptase-PCR, next generation transcriptome sequencing and bioinformatic analysis.

Eligibility

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

• British Council IELTS - score of 6.0 overall, with no element less than 5.5
• TOEFL iBT - overall score of 80 with not less than 17 in listening, 18 in reading, 20 in speaking and 19 in writing.

How to apply

To apply for this project applicants should complete an online application form and attach the following documentation to support their application.

• a full academic CV
• degree certificate and transcripts of marks
• Evidence that you meet the University's minimum English language requirements (if applicable)
• Evidence of funding

To help us identify that you are applying for this project please ensure you provide the following information on your application form;

• Select PhD in Biological Sciences as your programme of study
• Give the full project title and name the supervisors listed in this advert

For information about the application process please contact the Faculty Admissions Team:

e: fbsgrad@leeds.ac.uk

Funding Notes

This project is open to applicants who have the funding to support their own studies or who have a sponsor who will cover these costs.