Job ID: 87023

Funded PhD studentship: Molecular mechanisms for the biological alteration of behaviours by infection in mammals

Position: Ph.D. Student

Deadline: 15 September 2022

Employment Start Date: 10 October 2022

Contract Length: 3 years

City: Leeds

Country: United Kingdom

Institution: University of Leeds

Department: School of Biology

Description:

Supervisors: Dr G McConkey, Dr S Clapcote, Dr D Ulaeto

About the Project: The PhD project is on the impact of infection and environmental factors on animal behaviour, and will investigate the mechanism(s) responsible at the cellular and molecular levels. Infection has been associated with behavioural changes in animals, with pathogens that reach the brain among the most prominent. The zoonotic pathogen Toxoplasma alters the behaviour of its host during its chronic stages when it is found in the brain. Infected rodents lose their innate fear of cat odour (indeed it is reversed to attraction in some studies) and are hyperactive. This pathogen is one of the best known examples of a mammalian infection associated with a mental disorder; many studies linking it with schizophrenia. Infection with the COVID-19 virus SARS-CoV-2 can result in Long-COVID, affecting up to 10% of COVID cases with symptoms including fatigue, brain fog and impaired cognition. We are studying the effects of both these pathogens on neurophysiology and behaviour. Prior work in our group has found infection changes levels of specific neurotransmitters and induces epigenetic alterations modulating genes involved.

Neurophysiological changes will be investigated as well as the impact of neuroimmune changes. Moderation of neurotransmitters and hormones with infection will be assessed; as well as neuron architecture and dendritic spine morphology. 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, CRISPR-Cas9 engineered mutant mouse 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.

Key Words: neurobiology, infection, signalling, immunology, epigenetics, pathogen

Eligibility: Applicants should have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. A Master’s degree is desirable but not essential. 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.

How to apply: To apply for this scholarship opportunity applicants should complete an online application form available here https://biologicalsciences.leeds.ac.uk/research-degrees/doc/how-to-apply and attach the following documentation to support their application: a full academic CV, degree certificate, transcripts of marks, and evidence that you meet the University’s minimum English language requirements (if applicable). To help us identify that you are applying for this scholarship 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 source of funding please state you are applying for an advertised Faculty Scholarship Funding Notes.

References:

Alsaady et al. Downregulation of the Central Noradrenergic System by Toxoplasma gondii Infection. Infect Immun. 2019 Jan 24;87(2):e00789-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346129/

Laing et al. Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes. Trends Immunol. 2020 Dec;41(12):1072-1082. https://eprints.whiterose.ac.uk/168408/