PhD (Neuroscience) Manchester University, UK
MSc (Chemical Pathology), University of Cape Town, SA
Honours (Pharmacology), University of Cape Town, SA
BSc (Botany, Biochemistry), University of Cape Town, SA
My research focuses on the molecular/mechanistic understanding of how sex steroid signaling and neuroinflammation interact and contribute to striatal and cortical modulation of dopamine and how dopamine-related behaviours (psychotic-like symptoms, memory and cognition) are altered by sex steroids in male and female rats of different ages. The goal is to transfer this knowledge to human studies to develop or enhance sex steroid based and immune-related treatments for the cognitive and psychotic symptoms of schizophrenia in an age and gender specific manner.
2019-2021 (extended into 2022 due to COVID) NHMRC project grant (APP11603990). Purves-Tyson, Shannon Weickert, Meyers, Killcross. Determining the molecular underpinnings of improved cognition induced by estrogen receptor modulation $712K.
2023-2026, NSW Schizophrenia Research Grants Program . Dr Purves-Tyson, Prof Cornish (Macquarie University), Prof Bauman (UC Davis), A/Prof Moalem-Taylor (SBMS, UNSW) Unlocking midbrain microglia as treatment targets for dopamine dysregulation in schizophrenia. $1,000,000
Preclinical studies ask how sex steroid-related, dopamine-related (and other neurotransmitter systems) and immune-related gene and protein expression in the nigrostriatal, mesolimbic and mesocortical dopamine pathways are altered in the rat maternal immune activation (MIA) model of dopamine dysregulation in offspring with high and low inflammation. We can measure inflammatory molecules and sex steroids in the periphery and relate this to behaviour and to gene and protein expression in different brain regions. We can also do this in both sexes and longitudinally (i.e juvenile, adolescence, adulthood, aged). It is unknown whether schizophrenia patients move in and out of high inflammation status and how this relates to cognitive decline and psychotic episodes or how it is related to antipsychotic treatments or if it changes with changing circulating hormone levels. I will address these questions in the MIA model.
Significance: Understanding sex steroid-induced schizophrenia-related behaviours in the context of neuroinflammation and the dopamine neurotransmitter system in midbrain, cortex and striatum in both sexes will provide new knowledge that will lead to new treatment targets with a focus on individualized treatment (i.e. by sex and inflammatory status).
Post mortem Human brain Studies
The midbrain, although critical to dopamine regulation is surprisingly understudied in the context of schizophrenia, especially in the post mortem field. We use post mortem human midbrain from people that had schizophrenia during their lives and compare them to brains from people that had no neuropsychiatric diagnoses. Our research has identified dysregulation of multiple DA-related transcripts (Purves-Tyson, Translational Psychiatry 2017) and high and low immune groups in this cohort (Purves-Tyson, Molecular Psychiatry 2021, online 2019). As I identify further molecular targets in the MIA model, these will be interrogated in the schizophrenia midbrain cohort.
My Research Supervision
Honours: Effect of estrogen receptor modulation and maternal immune activation on dorsal striatal dopaminergic transcripts in adult rat offspring
PhD: The interaction between sex steroids and neuroinflammation and their role in the dopamine dysregulation in the maternal immune activation rat model underlying psychosis and cognitive deficits in schizophrenia