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postdoc

Congrats Phat on your first authored Nature Communications paper

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New discovery rewrites the rules of antigen presentation

Credit: Thinh-Phat Cao, Monash University.

A new discovery about how cells communicate with each other in the body’s immune system has revealed deeper insights for an international team of scientists into fundamental immune system function.

The new study, published in Nature Communications, overturns a long held understanding about how T cells – white blood cells that make up a key part of the immune system – recognise lipid antigens, a chemical class of molecules that make up cell membranes.

Lipids are presented to T cells by a distinct family of molecules called CD1, yet one member of this family, CD1c, has remained poorly understood despite its significant role in human immunity.

For more than 30 years, scientists considered that antigens were displayed to T cells in a simple, upright position, pointing directly towards the T cell. This “end-to-end” arrangement was considered a universal rule governing how immune cells recognise threats.

Now, researchers from Monash University’s Biomedicine Discovery Institute (BDI) and the Harvard-affiliated Brigham and Women’s Hospital, together with collaborators from the University of Melbourne and the University of Oxford, have challenged long-held assumptions about how immune recognition works.

Challenging rules in immunology

Using high resolution imaging the research team discovered that CD1c can display lipid molecules in an unexpected sideways orientation. Dr Adam Shahine, a NHMRC research fellow at Monash BDI, said the discovery reveals that antigen presentation is not governed by a single rigid set of rules, but instead can involve different arrangements that expand how the immune system surveys its environment.

“Much of immunology has been built around the idea that immune recognition follows one fixed arrangement,” Dr Shahine said. “This work shows that the immune system is more flexible than we assumed, and that there are additional ways immune cells can ‘see’ what’s around them.”

Rather than interfering with immune recognition, the sideways positioning allows T cells to scan CD1c effectively.

The findings show that CD1c can handle larger lipid molecules by allowing part of the molecule to extend out to the side, while remaining visible to T cells.

This new antigen display model does not merely hold for a single type of lipid. Dr Tan-Yun Cheng has demonstrated that mass spectrometry could be used to directly detect CD1c binding to dozens of lipid types, with the patterns of lipids displayed suggesting this new model could be broadly used in the CD1c system.

First author Dr Thinh-Phat Cao said that the findings highlight CD1c as a complex molecular player with unique properties in immune recognition.

“Using data collected at the ANSTO Australian Synchrotron, we found that CD1c can hold multiple lipids in place at the same time, in unique configurations, but can position them in a manner that still allows immune cells to engage,” Dr Cao said.

“That flexibility helps explain how the immune system can deal with such a wide variety of lipid molecules, shaping immune responses in unexpected ways.”

What this means for future breakthroughs on health and disease

Lipids are abundant throughout the body and play important roles in normal physiology and disease. Understanding how the immune system recognises these molecules is essential for building a more complete picture of immune function.

By revealing a new way lipids can be displayed to immune cells, the study helps explain how immune recognition can extend beyond traditional models based on proteins alone.

While this research is driven by fundamental discovery, it also lays important groundwork for future studies exploring how lipid recognition contributes to health and disease.

At Monash University, this work is supported by growing international collaborations, including through the Monash Boston Hub, which strengthens research connections between Australia and the United States.

By bringing together basic scientists and clinical researchers, these partnerships help ensure that foundational discoveries, such as this new understanding of lipid immunity, can be explored further in human disease over time.

Understanding this could lead to new strategies for diagnostics and targeted therapies.

“This discovery opens new avenues to better understand how diseases where lipids play a role,” Dr Shahine said.

“This could aid in the design of treatments that are better matched to how the body responds to disease.”

Read the full publication, “Sideways lipid presentation by the antigen-presenting molecule CD1c”, in Nature Communications: https://doi.org/10.1038/s41467-025-67732-2

This research has been supported with funding from the National Health and Medical Research Council and the Wellcome Trust.

Original article

Congrats Jamie and the international team on awarded funding for an 8-year research programme from global charitable foundation Wellcome Trust.

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A team led by Professor Graham Ogg, Deputy Director of the MRC Translational Immune Discovery Unit (TIDU) and Leader of the Translational Dermatology Unit, alongside Professor Jamie Rossjohn (Monash, Australia and TIDU Affiliate member), Professor Branch Moody (Harvard, USA), Professor Muzlifah Haniffa (Newcastle) and Professor Gurdyal Besra (Birmingham), have received a Wellcome Discovery Award to investigate how immune cells contribute to inflammation.

The research programme will be strongly collaborative, bringing together researchers with complementary skills from the co-applicant laboratories to address how T cells can specifically sense certain lipids which can be indicators of infection or tissue damage.

Immune cells help protect us from infections and other challenges, but can also contribute to different forms of inflammation if not adequately controlled.  T cells are a key type of immune cell that circulates in the bloodstream and can enter different organs to sense infection and damage.  By understanding how T cells are triggered, the research team aims to gain deeper knowledge about different forms of inflammatory diseases and how they might develop new approaches to treatment.

The Wellcome Discovery Award will also promote training and development opportunities and will facilitate interactions with patients, the public and scientific communities.  The discoveries will be made available in open databases, to enable the wider field and drive improvements in human health.

Original article

postdoc

Congrats Adam on your Cell paper

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Researchers create “Lipidomic Map,” offering insights into immunology

An international team of scientists has developed a method for simultaneously detecting thousands of lipid molecules that are displayed to T cells in the human immune system.

The study, co-led by Professor D. Branch Moody, MD, of the Division of Rheumatology, Immunity and Inflammation at Brigham and Women’s Hospital, and Adam Shahine, PhD, at the Monash Biomedicine Discovery Institute represents a collaboration among researchers from Oxford, United Kingdom, Monash University in Melbourne, Australia and Groningen, Netherlands. The results were published today in Cell.

The team developed a new and sensitive method to detect more than 2,000 lipids bound to CD1 antigen presenting molecules, which display antigens to the human immune system.

While scientists have long known that T cells recognise antigens, until the 1990s, it was thought that these antigens were always peptides derived from proteins. Because lipids are not encoded by genes and are instead made by enzymes and form into membranes, they have entirely different functions and positions in the cell.

The ability to measure many lipid antigens at one time will allow future researchers to cross-check any disease-related lipid of interest to the list of candidate lipid antigens from this map and potentially make connections to diseases.

Their efforts yielded the first integrated CD1 lipidomic map, which could help guide the investigation and discovery of lipid blockers and antigens for T cells and support the view that lipids normally influence immune responses.

The research builds on earlier methods that separate cellular lipids in one chromatographic system, which provided only a limited perspective. The new structural biology work, undertaken by Dr Shahine, ARC DECRA fellow, showed how lipids fit inside proteins using size-based mechanisms.

Combined, the structures and biochemistry detail rules about the size, shape, and chemical content of the kinds of lipids that can bind CD1 and cause a T cell response—either activation or deactivation. It is the latest in a series of studies that date back to the 1990s, when Brigham scientists discovered that T cells can recognise lipid antigens.

“Splashdown“. The image provides a prism for thinking about how oily antigens are recognized in aqueous solution. Four lipid presenting molecules, CD1a, CD1b, CD1c and CD1d, including a three dimensional CD1-lipid complex, fall toward the surface of a blue and watery environment surrounding a T cell. Image credit: Dr Erica Tandori.

“In this ambitious decade-long, multidisciplinary study, we have characterized the full spectrum of cellular lipids that can be displayed to T cells. Further, we have collated 25 years of structural biology data, as well as new data collected at the ANSTO Australian Synchrotron, to standardize the rules that govern the molecular mechanisms in lipid presentation” said Dr Shahine. “Our hope is that the data generated in this study will serve as a foundation for future research in the field of lipid mediated immunity.”

Professor Moody said, “The Brigham provides an environment where physicians and scientists from differing fields can collaborate. This multidisciplinary effort involved biophysical techniques related to mass spectrometry and biological techniques related to lipid chemistry. The lipids informed immunological outputs, and the mode of lipid recognition is proven through X-ray crystallography.”

Read the full publication in Cell, titled CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms

DOI: 10.1016/j.cell.2023.08.022.

Original article

Congrats Praveena on the award of the ARC DECRA

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Monash BDI early career researchers awarded more than $2m ARC DECRA funding

Five Monash Biomedicine Discovery Institute (BDI) researchers have been awarded $2.23 million under the 2023 ARC Discovery Early Career Researcher Award (DECRA) scheme.

Minister for Education, Hon Jason Clare MP, announced $85 million for 200 projects nationwide to support early career researchers under the DECRA scheme.

Researchers at the Monash BDI received five awards to support a diverse range of discovery research into nanobiotechnology, bacterial membrane remodelling, microbial life in the atmosphere, lipid-mediated T cell immunity, and understanding how T cells recognise and respond to foreign antigens.

“This success is a testament to the depth of excellence in our early career researcher cohort, and I congratulate this outstanding group of recipients,” said Professor John Carroll, Director of the Monash BDI.

The grants awarded to the Monash BDI are:

Project: ‘Molecular insights into lipid-mediated T cell immunity.’ Dr Praveena Thirunavukkarasu, Rossjohn Lab, awarded $421,485

This project involves the discovery of novel lipids produced by the microbiome that play a significant role in T cell-mediated immunity. Using a combination of cutting-edge technologies such as mass spectrometry, protein crystallography, immunology and biophysics, this project will elucidate the molecular factors that govern the interaction between the identified lipids and T cells. This innovative research will provide fundamental insights into the recognition mechanism of lipids by T cells at a molecular level, thus broadening our knowledge in the field of biological sciences. The expected research outcomes will increase Australia’s international research standing in this burgeoning area of lipid-mediated T cell immunity.

Project: ‘A novel bacterial secretion system for applications in nanobiotechnology.’ Dr Christopher Stubenrauch, Lithgow Lab, awarded $429,449

This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools for molecular machine discovery and identification of ways to adapt molecular machines for biotechnological applications. This work should enhance Australia-UK ties through collaboration, provide benefits toward nanobiotechnology and economic benefits through more efficient food production.

Project: ‘Bacterial membrane remodelling and the interaction with peptides.’ Dr Meiling Han, Jian Li Lab, awarded $450,241

This project aims to elucidate the fundamental mechanism of lipid remodelling in the Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplay between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and biophysical approaches. Novel knowledge will be generated to improve our understanding of how bacteria remodel their outer membrane in response to environmental stress. This will benefit the future design of much-needed antimicrobial strategies including products and technologies to target bacterial membranes.

Project: ‘Microbial life in the atmosphere.’ Dr Rachael Lappan, Greening Lab, awarded $454,741

This project aims to resolve the nature and basis of microbial life in the atmosphere, the largest but most unexplored potential ecosystem on Earth. The atmosphere plays a role in transporting microbes, but our understanding of resident atmospheric microbial communities and their role in global atmospheric processes is minimal. Using cutting-edge molecular and biogeochemical approaches, this project aims to identify true microbial residents of the atmosphere, understand their mechanisms for survival in this environment and explore their role in seeding newly formed environments. The anticipated outcomes include fundamental knowledge on atmospheric microbial ecosystems, and their influence on global atmospheric processes.

Project: ‘Redefining how T cell recognition drives T cell activation.’ Dr Pirooz Zareie, La Gruta Lab, awarded $470,789

This proposal aims to define the key mechanisms that determine how T cells recognise and respond to foreign antigens; a critical feature that defines effective immunity. To achieve this goal, this proposal will leverage multidisciplinary collaborations and innovative methods to understand how structural and biochemical features of T cell receptor recognition influence T cell mediated immunity and development. In turn, this project will facilitate further research and development in the burgeoning field of T cell biology and advance life science research in Australia. Furthermore, as T cell biology is relevant to all vertebrates, this research will greatly benefit the conservation of threatened animal species and agriculture.

The DECRA scheme is designed to expand the knowledge base and research capacity in Australia and to provide economic, commercial, environmental, social and/or cultural benefits for Australia.

A full list of the 2023 ARC DECRA recipients and their projects is available on the ARC website.

Read the ARC Media Release announcing the DECRA scheme recipients on 16 September.

About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

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