Mater researcher celebrates research trifecta

Friday 14 May 2021

Good things certainly come in threes for Mater Post-doctoral Research Fellow, Dr Stacey Bartlett. She is celebrating a trifecta of research success. 

Dr Bartlett’s research focus is on investigating the impaired immune response to bacterial and viral pathogens contributing to increased susceptibility to respiratory infections in type 2 diabetes (T2D). She works with different lung infections, such as tuberculosis (TB), respiratory syncytial virus (RSV), influenza and more recently COVID-19, to better understand the underlying immunological mechanisms for increased susceptibility of T2D patients to these infectious diseases.

Dr Bartlett’s run of research wins started with being published in Frontiers in Immunology, the leading peer-review journal in her field. This published research, GPR183 regulates interferons, autophagy and bacterial growth during Mycobacterium tuberculosis infection and is associated with TB disease severity, showed that a receptor for oxidised cholesterols is important for the immune regulation of infections.

This receptor, GPR183, was identified in patients who suffer from both diabetes and tuberculosis. Dr Bartlett and team members of the Infection, Immunity and Metabolism Laboratory under leadership of Associate Professor Katharina Ronacher found that individuals with a lower expression of this receptor in their blood had more severe disease on their chest x-rays.

“In essence, it showed a particular oxidised cholesterol can be protective against infections  by activating GPR183.

“This receptor works by controlling the replication of bacteria inside immune cells called macrophages. When it’s activated with a specific natural oxidised cholesterol, the macrophages are encouraged to start a process called autophagy, which reduces the growth of bacteria inside of the cells, even in the absence of antibiotics,” she said.

This Mater Research work conducted in the Translational Research Institute labs involved collaborators at The University of Queensland and international scientists from Denmark, South Africa and the United States of America.

Dr Bartlett’s second success involved sharing the results of this research with worldwide TB experts during the recent online Keystone Symposia— Tuberculosis: Science Aimed at Ending the Epidemic. Her short talk was titled GPR183 Oxysterol Axis is Dysregulated at the Site of Disease During M. tuberculosis Infection.

Rounding out her trifecta, Dr Bartlett has now won a Mater Early Career Researcher Biomedical Seeding Grant to expand her research focus to identify novel treatments for respiratory infections.

“We know that patients with diabetes are at increased risk of infectious diseases like influenza, tuberculosis and COVID-19— but the underlying metabolic and immunological mechanisms contributing to this increased susceptibility are still poorly understood.” 

Dr Bartlett will use her grant to address this critical knowledge gap with studies on diabetes patients and in pre-clinical models of diabetes.

“I’m honoured to receive this grant to conduct research under the supervision of Associate Professor Katharina Ronacher. We will investigate the role of GPR183 in immune dysfunction in blood from diabetes patients versus healthy controls. Further, we will validate in a pre-clinical model of diabetes the benefits of modulating the activity of this receptor to improve lung pathology and influenza infection outcomes.

“This project has the potential to develop new treatments targeting this receptor to ultimately improve infectious disease outcomes in patients with and without diabetes.

“While our research model covers influenza, we believe this approach is equally applicable to COVID-19 and plan to expand the project focus there in the future,” she said.