2023 RTP - Mechanism of co-aggregation of beta amyloid and amylin in Alzheimer’s disease

Curtin University, Australia

Updated: 10 months ago
Location: Perth, WESTERN AUSTRALIA
Deadline: The position may have been removed or expired!

Status: Closed

Applications open: 8/07/2022
Applications close: 18/08/2022

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About this scholarship

Clinical studies have shown that type-2 diabetes (T2D) is associated with an increased risk of dementia, including Alzheimer’s disease (AD) [1]. Both diseases feature the accumulation of protein aggregates (beta amyloid42 or Aβ42 in the brain in AD and amylin in the pancreas in T2D). Aβ42 and amylin can co-exist in AD brain and interact to form highly neurotoxic heterocomplex aggregates [2] with enhanced ability to permeabilize and accumulate in neuronal cells [1], demonstrating a novel mechanism underlying amylin’s pathogenic role in promoting neurodegeneration. Amylin has a normal physiological role in the brain and, therefore, is a target for developing non-aggregating analogue peptides for the treatment of AD. Recent findings have developed non-aggregating amylin analogues that have the ability to neutralize Aβ toxicity [3].
This project will make use of state-of-the-art computational biophysics approaches recently developed at Curtin to study the behaviour and interactions of amyloidogenic proteins. Molecular dynamics simulations will be used to investigate the interactions and their affinity between Aβ42 and amylin, the structure of the protein oligomers formed, as well as the interactions and structure of such oligomers when amylin is replaced with amylin analogues that co-aggregate with Aβ42. This will enable the characterisation of the mechanism of formation of toxic hetero-aggregates of these two proteins and the range of structures exhibited in solution, as well as a first opportunity to determine how non-aggregating amylin analogues act to block the aggregation of Aβ42.
References:
[1] Bharadwaj P, Solomon T, Malajczuk CJ, Mancera RL, Howard M, Arrigan D, Newsholme P, Martins RN, Role of the cell membrane interface in modulating production and uptake of Alzheimer's beta amyloid protein, Biochimica et Biophysica Acta (BBA)-Biomembranes (2018), 1860, 1639-1651 
[2] Bharadwaj P, Solomon T, Sahoo B, Ignasiak K, Gaskin S, Rowles J, Verdile G, Howard M, Bond CS, Ramamoorthy A, Martins RN, Newsholme P “Amylin and β-amyloid proteins interact to form amorphous heterocomplexes with enhanced toxicity in neuronal cells”, Scientific Reports (2020) 10, 1-14
[3] GL Dharmaraj, FD Arigo, KA Young, R Martins, RL Mancera, P Bharadwaj, Novel Amylin Analogues Reduce Amyloid-β Cross-Seeding Aggregation and Neurotoxicity, Journal of Alzheimer's Disease, (2022) 1-18 

An Internship opportunity may also be available with this project.


  • Future Students

  • Faculty of Health Sciences

  • Higher Degree by Research

  • Australian Citizen
  • Australian Permanent Resident
  • New Zealand Citizen
  • Permanent Humanitarian Visa

  • Merit Based

The annual scholarship package (stipend and tuition fees) is approx. $60,000 - $70,000 p.a.

 

Successful HDR applicants for admission will receive a 100% fee offset for up to 4 years, stipend scholarships, valued at $28,854 p.a. for up to a maximum of 3.5 years, are determined via a competitive selection process. Applicants will be notified of the scholarship outcome in November 2022. 

 

For detailed information, visit: Research Training Program (RTP) Scholarships | Curtin University, Perth, Australia.


Scholarship Details

1


All applicable HDR courses


BSc (Hons) or Master’s degree in biomedical sciences, chemistry, biotechnology or related fields. Experience is required in molecular modelling, molecular simulations and/or structural bioinformatics. Experience is desirable in high performance computing and programming. 


Application process

If this project excites you, and your research skills and experience are a good fit for this specific project, you should contact the Project Lead (listed below in the enquires section) via the Expression of Interest (EOI) form. ahead of the closing date.


Enrolment Requirements

Eligible to enrol in a Higher Degree by Research Course at Curtin University by March 2023


Enquiries

To enquire about this project opportunity that includes a scholarship application, contact the Project lead, Professor Ricardo Mancera via the EOI form above.



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