Antibody mimetics for synapse modulation

Development of antibody mimetic protein domains for intracellular modulation of synaptic function

Degree type

PhD

Closing date

18 July 2022

Campus

Hobart

Citizenship requirement

Domestic/International

About the research project

The project is part of the funded NHMRC grant (2021-2024) and will develop several antibody mimetic protein domains that can modulate the synaptic functions of neurons. Alteration of synaptic function is implicated in all neurological conditions and this either takes the form of reduced synaptic transmission or incorrect changes in synaptic strength. One of the key approaches to understand synaptic function is to experimentally manipulate proteins at the synapse but these often is done at transcription or translation level, or involves overexpression of exogenous altered proteins. The ability to be able to manipulate the native proteins expressed in the cells would provide a more accurate insight into understanding synaptic function and reflect the true functions of synaptic proteins. To do this, the project will develop single-domain antibody domain or fibronectin III domain based antibody mimetics that can be expressed intracellularly and bind to native synaptic proteins. In doing so, these proteins can either act as activator or inhibitors of the protein function directly, modified to alter the rate of degradation, or modified to be optogenetically or chemogenetically controlled. The goal of the project is first to establish a pipeline to develop the single-domain nanobody and fibronectin III domains based on mRNA- and phage-display approaches and develop the binders to the intracellular domain of BDNF receptor TrkB and calcium dependent phosphatase calcineurin. TrkB is implicated in long term potentiation and calcineurin is implicated in long term depression which are key mechanism of changing synaptic strength and believed to be the cellular basis of learning and memory formation. Once the 'hits' are identified, these protein domains will be validated in cell culture for selective binding in the cells and screen for functional disruption of these proteins. Ultimately, the some hits will be further developed as neuroscience tools to optogenetically alter synaptic plasticity.

Primary Supervisor

Meet Dr John Lin

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

  • a living allowance stipend of $28,854 per annum (2022 rate, indexed annually) for 3.5 years
  • a relocation allowance of up to $2,000
  • a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

If successful, international applicants will receive a University of Tasmania Fees Offset for up to four years.

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Additional eligibility criteria specific to this project/scholarship:

  • Applicants must be able to undertake the project on-campus

Selection Criteria

The project is competitively assessed and awarded.  Selection is based on academic merit and suitability to the project as determined by the College.

Additional desirable selection criteria specific to this project:

  • The desirable candidate should have demonstrated strong intellectual ability as reflected by strong academic performance in their undergraduate degree.
  • The candidate should have some background in chemistry, physics and/or engineering.

Application process

There is a three-step application process:

  1. Select your project, and check you meet the eligibility and selection criteria;
  2. Contact the Primary Supervisor, Dr John Lin to discuss your suitability and the project's requirements; and
  3. Submit an application by the closing date listed above.
    • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
    • As part of your application, you will be required to submit a covering letter, a CV including 2 x referees and your project research proposal.

Following the application closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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