Continuing our Researcher Profile series for 2022, Dr Maria Halili spoke with the Library about her research and her advice for early career researchers.
Dr Halili graduated with a Bachelor of Biotechnology (Honours) from the University of Queensland (UQ). She obtained her PhD in 2010 from UQ, working with Professor David Fairlie at the Institute for Molecular Bioscience. The focus of her PhD was investigating proteins involved in inflammation and using small molecules to regulate and inhibit inflammation in in-vitro settings. She joined Professor Jenny Martin as a post-doctorate researcher, with a focus towards developing novel antimicrobial compounds to combat antibiotic resistance in bacteria.
Dr Halili joined Griffith University in 2018, at the Griffith Institute for Drug Discovery. As a Research Fellow, she is continuing her research on antimicrobial compounds, using a variety of techniques such as structural biology, microbiology, biochemistry and fragment-based drug discovery.
What path led you to your research?
I have always been fascinated in how small molecules interact with host proteins to elicit a response. I was interested in the drug discovery aspect, looking for new molecules which have the potential to become useful drugs for pharmaceutical use. My undergraduate degree was a Bachelor of Biotechnology at the University of Queensland, majoring in Drug Discovery and Development. Developing a small molecule into a useful drug for clinical use can take up to 20 years and $1 billion! The process through which this happens was really interesting to me, especially the early-stage research.
I did a PhD looking for new molecules that act on proteins involved in inflammation, which is an immune response our body creates to defend itself against assault. If inflammation gets out of control, you end up with a disease state, like arthritis, asthma and even cancer.
After my PhD, I shifted focus to looking for new drugs to treat bacterial infections. This is important because we are running out of antibiotics that work against bacterial infections.
What projects are you currently working on?
Currently I am looking at proteins that are found in bacteria, which are important in host infection. These proteins are called virulence factors, and I am looking at how to regulate these proteins with small molecules. I am especially interested in developing new drugs that can treat infections caused by the bacterium Burkholderia pseudomallei, an especially hardy bacterium that is difficult to treat with current antibiotics. B. pseudomallei is found in soil. Floods, which we are currently experiencing, bring the bacterium to the surface and into the water. If you have a cut in your skin or accidentally inhale or swallow water, the bacterium can enter your circulation. Normally this is not a big deal, but if you have a weak immune system (for example, if you have diabetes or are elderly), this can cause sickness, from localised inflammation, pneumonia, to severe sepsis and even death.
I am also looking at developing methods to study membrane proteins for drug discovery, using a technique called mass spectrometry. Membrane proteins, found on the external part of a cell, come into contact with various regulatory proteins and other stimuli. Membrane proteins account for about 60% of all drug targets currently in the market. But they are difficult to work with, as they are hard to produce in large quantities in a stable configuration for drug discovery purposes. Mass spectrometry is a method which requires only a small amount of sample for analysis and can be a rapid method for screening small molecules that bind to a membrane protein.
‘Science can be frustrating at times, but it is fascinating, and you do get the eureka moments when you make an exciting discovery.’
Why is your research important?
Since the discovery of penicillin almost 100 years ago, antibiotic resistance has been known to develop quite quickly in bacteria. There have been several discoveries of new antibiotics, but within a few years of clinical use they have become useless in treating bacterial infection. Coupled with widespread use and misuse (such as treating viral infections with antibiotics which have no effect and antibiotics in livestock feed ending up in waterways), there are now bacteria strains resistant to all antibiotics. This can limit treatment options to drugs that can produce severe side effects. We need to combat antibiotic resistance in bacteria, otherwise we could be back in a world where a scratch from a fallen tree branch can once again be a cause of death.
The World Health Organization has recognized antibiotic resistance as a priority health area. However, pharmaceutical companies have by and large discontinued research into this field as it is not seen as profitable. So, it is up to us to come up with new strategies and new research towards combating what is to be the next global pandemic.
Who has inspired you?
Many people, but I have especially been inspired by the many women who have worked in the scientific field, which has in the past been dominated by men. From my supervisors, who have been supportive of me and my career choices to my colleagues and fellow early career researchers, who are forging successful careers while at the same time managing a household with young or school-aged children. I have three kids, so I work part-time. Doing research and juggling a family is challenging, and I am passionate about sharing my experiences and making sure that others in a similar position know that they are not alone, nor do they have to buckle under the pressure of supervisors demanding they work full-time.
What advice do you have for students and researchers?
Science can be frustrating at times, but it is fascinating, and you do get the eureka moments when you make an exciting discovery. You need to persevere and persist in what you are trying to achieve. Believe in yourself and your research! Look for mentors who can help you not just with experiments, but who are able to support you in your career path and help guide you.
