Before Dr Amy Wyatt even starts her research project in June 2016, the Illawarra Health and Medical Research Institute-affiliated scientist has already beaten the odds.

She was one of only three University of Wollongong researchers to attract a National Health and Medical Research (NHMRC) Project Grant in 2015 as lead investigator and one of just 515 successful applications from a field of 3,758, which equates to a success rate of just 13.7 per cent.

In the New Investigator sub category, she was one of only 10 women Australia-wide to receive an NHMRC grant (valued at $461,496) and when you also factor in her age, which is 33, and consider the fact that the average age of successful Project Grant applicants was 48.1, you get some insight into what a huge achievement this is (and she wrote the grant application while on maternity leave).

Dr Wyatt is no stranger to winning grants. In 2011, she won a coveted NHMRC CJ Martin Early Career Fellowship, giving her the opportunity to spend two years working in the laboratory of renowned biochemist and University of Cambridge (UK) researcher, Professor Christopher Dobson, who has authored or co-authored over 650 papers, more than 30 of which have been published in Science and Nature.

In fact, over the course of her short career, Dr Wyatt has been awarded more than $1M in research funding.

Protein misfolding

Her research focuses on the relationship between protein misfolding and inflammation in disease.

Most complex biochemical processes taking place in living organisms depend on the ability of protein molecules to fold into specific three-dimensional structures which serve to bring key functional groups together and keep everything in balance.

When proteins fail to fold correctly, or become misfolded, toxic aggregates can build up and lead to the development of a wide variety of diseases including late-onset diabetes, Alzheimer’s and Parkinson’s diseases and Motor Neurone Disease (MND).

While a great deal is already known about the processes that control the folding state of intracellular proteins, Dr Wyatt’s research also looks at extracellular protein homeostasis (proteostasis), a field pioneered by her former supervisor, Senior Professor Mark Wilson.

What she’s really interested in is the role of hypochlorite, an oxidant commonly known as bleach. Hypochlorite is produced by the body during inflammation and is thought to promote protein misfolding.

By working in collaboration with local, national and international researchers, Dr Wyatt is trying to identify the molecular systems that influence this process.

Under Professor Dobson’s and Wilson’s guidance, she made a significant discovery in 2014 when she identified the unique relationship between hypochlorite and alpha-2-macroglobulin (A2M), a chaperone protein that is particularly important when the body is in an inflammatory state.

In the prestigious journal, Proceedings of the National Academy of Sciences USA, the team reported that by chemically modifying A2M with hypochlorite they could dramatically increase its ability to sequester misfolded proteins; a discovery which might one day lead to the development of a drug that can switch on the chaperone activity of A2M to provide greater protection when it is needed.

Early Career Fellow

Over the past three years, Dr Wyatt has been employed by Professor Wilson as a post-doctoral researcher working in IHMRI’s laboratories (with some time off for maternity leave and part time work).

Now that that contract is complete, she will lead the NHMRC-funded project entitled: ‘The effect of hypochlorite on the toxicity and clearance of the Alzheimer’s disease -associated amyloid beta (Aβ) peptide’ (Aβ being the main component of the amyloid plaques found in the brains of Alzheimer patients).

While primarily focused on Alzheimer’s disease, the work will extend into investigations on whether or not hypochlorite-induced protein misfolding is implicated in other disorders such as arthritis, atherosclerosis (heart disease), MND and Parkinson’s disease.

Another fascinating area into which Dr Wyatt’s research will venture is into the realm of pregnancy, as protein misfolding has recently been implicated in pre-eclampsia, a life-threatening disorder characterised by high blood pressure and a large amount of protein in the urine.

With IHMRI cancer specialist, Professor Marie Ranson, she will investigate two newly identified pregnancy-associated chaperones as part of the grant.

Dr Wyatt’s ability to write and speak about her research goes some way to explaining how and why she has been so successful to date. With Professor Wilson, she recently won the UOW’s iAccelerate pitch competition (for a presentation entitled, ‘A novel half-molecule strategy to combat inflammatory disorders’) and, while appearing simultaneously humble and confident, she is able to clearly explain often complex science.

This ability has, in part, been honed by her time in the theatre. Indeed, as a student she directed and performed in several plays but her busy research career, coupled with the fact that she has a young child, has put paid to that.

The right environment

Being able to include ‘Chief Investigator’ on her CV is certainly a major achievement, but it comes with huge responsibilities, from managing research students and staff to attending national and international conferences, to accepting invitations to contribute to the activities of the NHMRC National Dementia Research Institute as well as an NHMRC grant review panel – prestigious opportunities for researchers at any level.

While relishing these opportunities, she says juggling a busy research career with parenting remains a major challenge for many researchers.

“Typically women are under-represented in academic research and the limited funding that is available tends to go to established researchers based at major metropolitan universities. I am excited to have the opportunity to start my own research group here at IHMRI and very grateful to have this opportunity right here in my home town,” said Dr Wyatt.

“My career has already benefited a lot from the collaborative environment here at IHMRI and in particular, the mentorship I receive from Professor Wilson and other senior members of the Proteostasis and Disease Research Centre. I am also inspired by the enthusiasm of the many students involved in our projects. Being in a positive research environment is part of the NHMRC’s Project Grant criteria, so this is important not just on a personal level, but a professional one.

“I’m really happy that I can continue my research here over the next three years and I hope that collectively, IHMRI researchers will continue to break new ground in proteostasis research to attract even more funding to the Illawarra.”