An in vivo systems approach to understanding healthy cognitive aging across the life course

Populations are currently ageing, as we age a number of processes naturally decline including cognition, this presents a number of societal, healthcare and scientific challenges. One of the most feared aspects of getting old is age-dependent memory impairment (AMI) (Niccoli and Partridge 2012). We have shown the fruitfly, Drosophila like humans display AMI with wildtype flies showing a significant loss of memory after 20 days (Cavaliere et al, 2013). A single pair of neurons regulates memory centres in the fly brain that are important for memory consolidation as well as AMI (Tonoki and Davis 2012). Recently this highly defined circuit has also been shown to be important for control of sleep (Haynes et al, 2015). Sleep promotes memory consolidation in humans and flies. Furthermore when humans and flies age their sleep becomes fragmented and shifts from night to daytime sleep. It has recently been found that enhancing sleep can improve memory defects in learning mutants, aged and Alzheimer disease models (Ju et al 2014; Dissel et al 2015; Donlea et al 2014a; Donlea et al 2014b).

In this PhD project you will be trained in a broad range of Drosophila in vivo and interdisciplinary research techniques aimed at better understanding the interplay between sleep, memory and aging. These will include:
1) In vivo optogenetic and electrophysiological recordings of the relevant neurons during consolidation, across sleep-wake cycles and through the flies’ life.
2) Using these measurements of neural activity to generate computational models of the membrane potential and ionic currents that occur during memory consolidation, sleep and aging.
3) Performing transcriptomic analysis to understand the molecular changes that occur:
a) Pre versus post memory consolidation
b) In sleep versus wake cycles
c) In young versus old flies.
4) These approaches will refine our models generating hypotheses to test by identifying the key membrane signalling events and molecules predicted to switch neurons from naïve to consolidated, from sleep to awake and from young to old. These will be tested with a range of experimental approaches including measuring predictable changes in behaviour. Ultimately this approach may allow the experimenter to implant memories into the fly without training or optogenetically switch the fly between sleep to wakefulness and between cognitively young and old.

To apply for a SWBio DTP project at the University of Bristol, you need to choose: Faculty of Biomedical Sciences under the ’Faculty’ section, and South West Biosciences Doctoral Training Partnership (PhD) under the ’programme choice’ section. Additionally under the ’Research Details’ section, please indicate that you are applying for a SWBio DTP funded project and give the project title and names of supervisors. For eligibility information: http://www.bristol.ac.uk/swbio/apply/eligibility.html

Deadline for applications: MIDNIGHT on Tuesday 1st December