Please tell us about yourself

When you have experienced the almost immediate, transforming effect of antibiotics at a time when you’re feeling your absolute worst, it’s not something you forget.

Particularly the next time you’re feeling a whole new level of absolute worst, and your doctor won’t hand you the antibiotics you’re certain you need.

But we are now paying the price for swapping get better soon with get better right now, and the result isn’t just personal frustration at our GP who won’t “cure” our sore throat.

We are now in the grips of a very real crisis of global antibiotic resistance. The Medical Journal of Australia has predicted that by 2050, deaths from currently treatable infections will overtake all cancer deaths, due to the over-prescription of antibiotics.

Original Link:

https://chemistry.anu.edu.au/news-events/news/meet-anu-chemist-fighting-frontline-antibiotic-resistance

“When I was a kid, I would go to the doctor and come home with a big bottle of pills,” Dr Lara Malins, a Research Fellow from the ANU Research School of Chemistry, remembers.

Malins is a native of Hawaii, but moved to Australia in 2010 to complete her PhD at the University of Sydney. Her postgraduate studies in the group of Professor Richard Payne first sparked her interest in peptides. Prior to beginning her PhD, Malins worked in a research laboratory on small molecule synthesis, developing new ways to build molecular complexity from simple chemical precursors. However, she had never tackled molecules as large or as intricate as proteins.

How did you end up in such an offbeat, unconventional and unique career?

Fast forward to 2015, and Dr Malins has another, related, memory: hearing the World Health Organization put out a call to action on antibiotic resistance.

“They essentially said we don’t have many antibiotics left that can treat the most resistant bacteria and in fact we’re finding strains that are resistant to all antibiotics that we have.

“So they wanted to mobilise everyone: doctors need to prescribe antibiotics less, patients need to comply better with their therapies.

“I saw I had the training and skills to be helpful in this fight, because one of the under-explored areas of combatting antibiotic resistance is to develop new drugs that have new modes of action and can potentially outsmart resistant bacteria.”

Dr Malins is a chemical biologist, meaning her research applies the methodology of chemistry towards molecules of biological interest, in her case, proteins and peptides.

“Proteins and peptides are becoming increasingly important therapeutics,” she explains.

What did you study?

I did my PhD in Chemistry from University of Sydney.

Tell us about your career path

“Coming in to the PhD, the idea of applying my skills to peptide and protein synthesis was really interesting and attractive to me.” Malins was particularly inspired by the prevalence of proteins in nature and in the human body: “They’re responsible for all sorts of biological functions, and at the same time, numerous disorders are linked to abnormalities in protein expression or to the types of modifications that the proteins present. The idea that one could use chemical synthesis to probe questions on a biological scale was really exciting to me.” In pursuit of this goal, Malins completed her PhD studies in peptide and protein synthesis, exploring cancer vaccines and a number of bioactive peptides.

Malins continued her focus on peptide synthesis when she moved to The Scripps Research Institute in San Diego following her PhD, and hopes to further her studies when she comes to the ANU in October this year. After some settling in, Malins aims to build a strong team and apply her knowledge to tackle one of the globe’s biggest health issues.

“Antibiotic resistance is a huge problem globally,” Malins explains. “A couple of years back, the World Health Organisation sent out a call to action that essentially said, “we need everybody on board to develop new therapies, new means of detection, and new ways of helping people stay with the regime of prescribed antibiotic use.”

Malins thinks peptides can help with this urgent need, particularly in the area of drug development. But that means first solving some fundamental issues.

How does your work benefit the community?

The development of antibiotics has been essential to the massive advancements we’ve seen in medicine and health over the last century. However, antibiotic-resistance is leading many to fear we are entering a ‘post-antibiotic’ world, potentially returning us to a time where the most basic illnesses could kill once again. Through her work on synthetic peptides, future RSC researcher Lara Malins is hoping to combat this problem.

“My goal is to use synthetic methods to understand the biological role of peptides and proteins and also to exploit their inherent biological activity to develop new antibiotic therapies.

“I’m looking at a particular type of peptides called ‘lantibiotics’ which are a very complex class of modified peptides that have promising activity. But they haven’t really seen their therapeutic potential realised yet because we have trouble making them in the lab. They’re a bit funky and have a variety of unnatural linkages that exist in nature, but that we don’t yet know how to replicate.

“If we can find new strategies to make them in the lab to explore their antibacterial and antibiotic activity, it would be a huge step forward in this fight against antibiotic resistance.”

Right now Dr Malins says her research is “about learning absolutely everything we can.”

“In your mind you have a vision that one day this is going to be a really great therapy but there’s a lot of time between the discovery, and that realisation.”

In the meantime, we’ll just have to toughen up and endure our sore throats. Or risk discovering a whole new level of absolute worst, on a global scale.

How does Chemistry help in your line of work?

“There are a lot of unresolved problems with peptide drugs,” Malins explains. “Your body has many naturally-occurring peptides, but they’re often degraded very quickly.” The efficacy of peptides, as Malins describes, results from their ability to combine with very specific targets and modulate specific biological responses. As therapeutics, however, a lack of stability may mean that the peptide drug never makes it to its target site. Innovative chemistry may help slow the degradation of peptides in the body.

“Part of my goal is to use synthetic methods, organic chemistry mainly, to modify peptides—keeping their function and biological activity, but making them more stable. There are a number of strategies that one can pursue, including cyclization of the peptide, or modification of the residues of the peptide backbone. These changes may alter the molecule so that it becomes a more suitable therapeutic.”

Using these techniques, Malins hopes to develop new peptide-based antibiotics.

“Chemistry can really contribute to the development of new therapies. There are some promising peptide antibiotics, but they’re currently very difficult to synthesise. While we can isolate them in small quantities, we can’t modify them very easily because we’re limited by what nature has produced. An alternative, however, is to develop a new, ‘ground up synthesis.’ By preparing a peptide from scratch in the laboratory, we can insert modifications, fine tune the biology, and also make the molecule more stable and more drug-like. That’s one of my primary research aims when I arrive at the ANU—trying to tackle the issue of antimicrobial resistance through the design of new peptide antibiotics.”

In doing so, Malins will hopefully take her work in the lab to a global stage, helping us deal with an incoming post-antibiotic world that could be a health disaster.