Research focus
Midlife obesity and diabetes substantially increase the risk of dementia, but the mechanisms are unknown. In my current position in the Merkle laboratory I am attempting to understand the influence of obesity and diabetes on neurodegenerative processes and how these could be exploited to identify tractable drug targets
Background and experience
I initially trained in Pharmacology at the University of Manchester. My course included a year’s experience in drug discovery at GlaxoSmithKline. I then completed my PhD in Neuroscience at Imperial College London in 2017, focusing on the hypothalamic circuitry in relation to sleep, thermoregulation and sedative drugs. I moved to the Institute of Metabolic Science in 2020 to pursue pre-clinical research into dementia and metabolic disease.
Working at the IMS-MRL
My research strategy has three components:
1) Understanding mechanisms that connect obesity and diabetes to neurodegeneration
2) Repurposing ‘old’ drugs as new treatments for dementia
3) New methods for automated and unbiased in vivo validation of new therapeutics
I primarily work with prion-induced neurodegenerative models combined with automated behavioural testing and “omics” technologies, including RNA-sequencing, lipidomics and peptidomics, as well as biochemistry, histology, multivariate analysis and machine learning.
My current work builds upon my doctoral studies, which focussed on neuronal circuits of the hypothalamus which control autonomic behaviours including the regulation of temperature and the initiation of non-rapid eye movement (NREM) sleep. Over several years, I developed methods to identify temperature-sensitive neurons in the preoptic hypothalamus of mice. I was the first to identify that nitrergic warm-active neurons connect temperature sensing to NREM initiation (Harding et al, Curr Biol, 2018). Consequently, it appears that one function of sleep is to modulate energy expenditure (Harding et al, Front Neurosci, 2019, Harding et al, Curr Opinion Physiol, 2020). I have since shown, using in vivo fibre photometry, that these same neurons are specifically NREM and REM active and necessary for normal sleep structure (Harding et al, Front Neurosci, 2021)
