Project Title: Investigation of the role of astrocytes in encoding circadian function and their mis-regulation in Alzheimer’s disease
Supervisor: Dr Marco Brancaccio
Location: Burlington Danes Building, Hammersmith Hospital Campus
I have been awarded an Imperial College President’s PhD scholarship to investigate astrocytic circadian function and its mis-regulation in the early stages of Alzheimer’s disease in the Brancaccio laboratory.
Prior to joining the UK DRI, I studied Natural Sciences at Trinity College Dublin, in which I specialized in Genetics. Here, I developed a strong interest in neural function and neurodegeneration. Upon completing my undergraduate studies, I joined Imperial College for an MRes in Bioengineering in the Schultz lab. In my research project, I made a computational model of the hippocampal CA1 network and showed that synapse loss was sufficient to produce the place cell abnormalities observed in experimental models, which have been shown to underlie navigational deficits in Alzheimer’s Disease.
MRes in Bioengineering (Distinction) from Imperial College London
BA in Natural Sciences (Genetics) from Trinity College Dublin
I am interested in the time-keeping mechanisms underlying rhythmic changes in physiology and behaviour and their dysregulation in neurodegenerative diseases. My research project focuses on understanding the role of astrocytes of the suprachiasmatic nucleus (SCN) as drivers of circadian rhythms.
Circadian dysfunction and sleep disruption are strongly associated with Alzheimer’s Disease, via increased levels of toxic proteins in the brain. Understanding the mechanisms underlying this association may thus be critical to identify new therapeutic targets to enhance clearance of neurotoxic proteins in Alzheimer’s Disease. Astrocytes mediate clearance of toxic brain waste, suggesting that they may be a key link between chronodisruption and neurodegeneration.
To elucidate the role of astrocytes in circadian function and their mis-regulation in Alzheimer’s Disease, my project will combine ex vivo and in vivo approaches to investigate astrocytic and neuronal circadian activities in pre-clinical models of Alzheimer’s Disease.
Ness N, Schultz SR (2021) A computational grid-to-place-cell transformation model indicates a synaptic driver of place cell impairment in early-stage Alzheimer’s Disease. PLoS Comput Biol 17(6): e1009115. https://doi.org/10.1371/journal.pcbi.1009115
Brancaccio M, Wolfes AC, Ness N (2021) Astrocyte Circadian Timekeeping in Brain Health and Neurodegeneration. In: Engmann, O., Brancaccio, M. (eds) Circadian Clock in Brain Health and Disease. Advances in Experimental Medicine and Biology, vol 1344. Springer, Cham. https://doi.org/10.1007/978-3-030-81147-1_6