Lipid droplets are exploited by pathogens that invade cells and then use the cellular lipid droplets as a source of fats. Professor Rob Parton and his team received a Human Frontier Science Program (HFSP) grant to explore the possibility that lipid droplets might also be a crucial form of defence against pathogens. International collaborative networks have allowed access to techniques and expertise. They have also facilitated mentoring and collaboration for students and early career researchers.
Professor Rob Parton (Image: University of Queensland)
2015 - Grant Awardees - Program Grants
Mammalian lipid droplets: a central role in the organismal antibacterial response?
Professor Steven P. Gross
Department of Developmental and Cell Biology, UC Irvine
Professor Albert Pol
Cell Compartments and Signaling, The August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona
Professor Robert Parton
Institute for Molecular Bioscience - University of Queensland
Professor Patricia T. Bozza
Lab. of Immunopharmacology - Instituto Oswaldo Cruz - Rio de Janeiro
Read more in the abstract.
Please describe the research project you undertook with the funding offered by HFSP?
In my career I have been fortunate to receive four separate HFSP grants for international collaborative projects in distinct scientific areas and with four different teams. In the latest grant we investigated whether lipid droplets, cellular organelles with a primary role in storing lipids, might play a new role, as a cellular defence against pathogens such as bacteria.
How did this funding program enable you to undertake your research?
At the time we started this we were not sure of success – it was an ambitious ‘blue-sky’ project, and very difficult to fund from other sources. It also required an international team, and a team with different types of expertise bringing new methods and ideas. Our proposal brought in expertise in biophysics (USA), immunology (Brazil), metabolism (Spain) and my own expertise in cell biology and imaging. This international project would not have happened without funding from the HFSP.
How has collaborating with international researchers supported your research effort and your research career?
Having worked in the UK, Germany, and Australia, I have been fortunate enough to interact with a great network of top researchers all around the world. To do the very best science we cannot be limited by geography – we must collaborate with the best in the world to make sure we answer the most important scientific questions and by using the right methods.
This is what I have always tried to do – I have numerous overseas collaborations and my papers all have international authors from all around the globe. These collaborations have made a huge contribution to my research career.
What are the advantages of collaborating internationally, both scientifically and for developing professional relationships/networks? Are there any challenges?
Our international collaborative networks allow us access to techniques and expertise not available in my own group. In addition to the obvious scientific benefits, we have formed networks of mentoring and collaboration for our students and early career researchers. Exchange of reagents and samples between countries can offer some challenges but the benefits far outweigh the frustrations.
What have been the outcomes of the research?
We discovered that lipid droplets, well studied as cellular structures that store lipids, have anti-bacterial activity. When we started the project, we already knew that lipid droplets were exploited by pathogens that invade cells and then use the cellular lipid droplets as a source of fats (eg. for energy).
We speculated that maybe lipid droplets were not always advantageous for bacteria but might have evolved as a form of defence – tempting the bacteria with their stores of fat but then killing the bacteria and protecting the organism. Some earlier work from our team members had provided hints from studies of flies but there was no evidence that such a defence mechanism might work in mammals.
The HFSP project led to the discovery that in fact there are a set of defensive agents recruited to lipid droplets upon bacterial infection. The lipid droplet associates with the invading bacteria to deliver its defensive arsenal, killing the bacteria to prevent infection.
What have been the longer lasting benefits of this HFSP grant and working with international networks?
The HFSP grants provide funding for three years but the projects that are nucleated in that period extend far beyond the lifetime of the grant. Our HFSP-funded research has created a new field of lipid droplet-mediated defence which will form the basis of our research for many years. Through the HFSP grant we have discovered a hitherto unexpected new form of innate immunity. With antimicrobial resistance an increasing global issue these new findings lay the groundwork for novel anti-infective strategies.
Electron microscopy image showing a lipid droplet (pseudocoloured purple) interacting with an invading bacterium (red). (Image: Professor Rob Parton)
Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense M. Bosch et al., Science, Vol. 370, No. 6514, 16 October 2020. DOI: 10.1126/science.aay8085
Immiscible immunity. Green DR., Science. 2020 Vol.370
Fat stores in our cells also hold immune proteins to fight infections, New Scientist October 2021, Michael Marshall
Lipid droplets and the host-pathogen dynamic: FATal attraction? Bosch M, Sweet MJ, Parton RG, Pol A. Journal of Cell Biology, 2 August 2021; 220
Review: biogenesis of the multifunctional lipid droplet: lipids, proteins, and sites. Pol A, Gross SP, Parton RG. Journal of Cell Biology, 3 March 2014; 204
Professor Robert Parton is Head of the Division of Cell and Developmental Biology and a group leader in the Institute for Molecular Bioscience and Deputy Director of the Centre for Microscopy and Microanalysis at the University of Queensland. Parton is internationally renowned for his pioneering work on the plasma membrane organisation of mammalian cells. His fundamental scientific discoveries, including the identification and functional characterisation of novel proteins involved in plasma membrane organisation, have far-reaching importance for diverse areas of biomedical research, ranging from the molecular mechanisms of lipid regulation and membrane morphogenesis, to liver regeneration, obesity, and cancer.