Manipulation of neuroimmune responses and behaviour by infectious agents

Summary

The School of Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.

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.

References:

1. Pairo-Castineira, E., Rawlik, K., Bretherick, A.D., QI, T., Wu, Y., Nassiri, I., McConkey, G.A. et al. (2023) GWAS and meta-analysis identifies 49 genetic variants underlying critical Covid-19. Nature 617:764–768 https://doi.org/10.1038/s41586-023-06034-3
2. Tedford, E., Badya, N., Laing, C., Asaoka, N., Kaneko, S., Filippi, B., & McConkey, G.A. (2023) Extracellular Vesicles Secreted by Infection Induce Transcriptional and Epigenetic Changes in Neurons, Nature Scientific Reports 13:6913 https://doi.org/10.1038/s41598-023-34074-2
3. Laing, C., Blanchard, N. & McConkey, G.A. (2020) Noradrenergic Signalling-Neuroinflammation Cross-talk Regulates Toxoplasma gondii-Induced Behavioral Changes. Trends in Immunology 41(12):1072-1082.
4. Deuchars, J., New, L., Yanagawa, Y., McConkey G.A. & Deuchars, S. (2023) Gabaergic regulation of proliferation within the adult neurogenic niche of the spinal cord. Neuropharmacology 223:109326.

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. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.