Project Description
Background and Aims
Much of the efforts to identify neuronal connections and map the ‘connectome’ of the nervous system focuses on synaptic connections between neurons. However, it is clear that these direct ‘wired’ connections formed from synapses make up only part of the network, and that ‘wireless’ connections involving neuromodulators such as neurotransmitters/neuropeptides play critical roles in the nervous system (1). Neuromodulators allow neurons to communicate that are not directly connected to each other, and can be at a distance from one another. These wireless signals have been shown to regulate several important behaviours and behavioural states (2,3).
Conventional methods to identify neuromodulator-dependent circuits have relied on genetic tools (gene knockout, transgenic re-expression, transcript knockdown), which, although instructive for many biological studies, lack information of the real-time dynamics of signalling. The goal of this project is to visualise how neuromodulators activate neurons in specific neural circuits using fluorescence biosensors that are able to reveal specific neuromodulator-receptor interactions with high spatiotemporal resolution. Many of these recently generated tools have tested in tissue culture and animal models, but not in C. elegans (for example (4, 5, 6)). This project will also aim to directly link real-time neural circuit activation with the onset of specific behaviours, which can be captured using simple video recording and behavioural tracking. Moreover, this project will use the information provided through directed evolution of dopamine and norepinephrine receptors to make ligand-directed biosensors, to generate analogous sensors for specific neuropeptides shown to play important roles in C. elegans.
This research, funded by the Australian National Health and Medical Research Council, will provide powerful knowledge on how ‘wireless’ signals work together with synaptic connections to drive important behaviours. Such transitions between behavioural states are critical for survival in almost all animals, meaning that transformative outcomes from this project have the potential to advance knowledge on a fundamental role of the nervous system, and can also be applied to translational medical problems such as defects in learning/memory and neurodegeneration.
Students interested in applying, please note the following selection criteria:
Essential
• Undergraduate (Bachelor’s) degree in the Sciences, with strong background knowledge in genetics and molecular biology.
• Must have completed a thesis for a laboratory research project (e.g. Honours, Masters or equivalent)
• Applicants must also meet the University requirements for English language proficiency.
Desirable
• Experience with microscopy and molecular biology
• Experience with C. elegans is a bonus but certainly not required.
About the lab and supervisor
The Chew lab at the University of Wollongong was formed in 2019, and from 2020-2024 will be funded by an Investigator Grant from the National Health and Medical Research Council (Australia). Our research vision is to map neuromodulator networks in the nematode worm C. elegans and to link these networks to learning/memory and experience-dependent behaviours. Dr Chew obtained her PhD from the University of Sydney, and was an EMBO Fellow during her postdoctoral research at the MRC Laboratory of Molecular Biology, Cambridge UK.
References
1) Bentley et al., 2016. PLoS Computational Biology.
2) Chew et al., 2018. Neuron.
3) Chew et al., 2018. Philosophical Transactions of the Royal Society B.
4) Patriarchi et al., 2018. Science.
5) Sun et al., 2018. Cell.
6) Feng et al., 2019. Neuron.
IMPORTANT: Please include with your application 1) an updated CV including the contact details of 2 academic referees and 2) a personal statement (200-300 words) indicating your research interests and motivation for joining the team.
Funding Notes
Fully-funded PhD project – Scholarship includes the cost of tuition fees and a tax-free stipend for the duration of the project at the Research Training Program (RTP) rate, currently at $27,596 (AUD) per year.
Domestic (Australian and New Zealand citizens/permanent residents) and International applicants are welcome to apply. Note for international applicants that visa fees and the process of visa application are the responsibility of the applicant and not of the University.
References
https://www.ncbi.nlm.nih.gov/pubmed/30146306
https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0368
You can contact Dr.Chew for if you are intested: ylchew@uow.edu.au
