Congrats Praveena on the award of the ARC DECRA

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 ThirunavukkarasuRossjohn 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 StubenrauchLithgow 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 HanJian 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 LappanGreening 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 ZareieLa 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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Congratulations Jamie – elected to The Royal Society

Professor Jamie Rossjohn, one of Australia’s leading scientists, has been elected as a Fellow of the Royal Society (FRS) – one of the world’s most prestigious scientific bodies – in recognition of his transformative contributions to science.

The Royal Society, established in the 1660s, is the oldest scientific academy in continuous existence in the world. During Monash’s 70-year history, Professor Rossjohn is only the second Monash University researcher to receive this international recognition.

Professor Rossjohn FRS, from the Biomedicine Discovery Institute at Monash University, is among 62 exceptional scientists honoured with Fellowships in 2022, joining the ranks of the world’s most eminent scientists. Previous Royal Society Fellows include Charles Darwin, Peter Doherty, Dorothy Hodgkin and over 280 Nobel Laureates.

A greater understanding of immunity has led to rapid advances in the development of vaccines and new cancer immunotherapies.  Developing groundbreaking and sustained discoveries that advance our molecular understanding of the immune system, Professor Rossjohn has made a pioneering contribution to natural knowledge and greatly enhanced Australia’s international reputation and capability for scientific discovery.

Professor Rossjohn’s citation says:

‘Professor Jamie Rossjohn is principally known for his contributions to the understanding of disease and the vertebrate host response, both from the aspect of protective and deleterious immunity. Namely, he has used structural biology to understand how T cell receptors recognise peptides, lipids and metabolites. Specifically, he has unearthed structural mechanisms of Major Histocompatibility Complex (MHC) polymorphism impacting on viral immunity, drug and food hypersensitivities and T cell mediated autoimmunity.

Rossjohn has pioneered our molecular understanding of how T cells bind lipid-based antigens presented by the CD1 family. He has elucidated the structural basis of how vitamin B metabolites are presented by the MHC class I related protein, MR1; this revealed an entirely new class of antigen for T cells.’ 

“Ultimately these basic discoveries may lay the foundation for future innovative immunotherapies to treat disease,” Professor Rossjohn said.

“I view this appointment as a broader recognition of the team’s efforts in discovery science over the last two decades since I joined Monash – the team of researchers who undertook the investigations, the national and international collaborative team, and team Monash,” Professor Rossjohn said.

“Monash was broad-minded enough to give me an opportunity as a new lab head and provided an ideal environment that has enabled my basic research program to thrive.”

Monash University President and Vice-Chancellor Professor Margaret Gardner AC congratulated Professor Rossjohn for his election to the Royal Society, which recognises his outstanding work over many years.

“Professor Rossjohn is an innovative and collaborative scientific leader whose contributions have had broad and profound impacts on scientific understanding of some of the most complex medical issues of our time,” Professor Gardner said. “This Royal Society Fellowship is well-deserved recognition of his remarkable work.”

Deputy Dean of Research for the Monash Medicine, Nursing and Health Sciences faculty, Professor James Whisstock says: “This is a wonderful and incredibly well-deserved honour for Jamie – we are all absolutely delighted for him.  Jamie and his team have used sophisticated structural biology techniques to revolutionise our understanding of the molecular mechanisms of the immune response.  His work has further had a profound impact on how some of the most devastating auto-immune diseases develop.”

Director of the Monash Biomedicine Discovery Institute,  Professor John Carroll says: “Jamie being elected as a Fellow of the Royal Society is fabulous recognition for a stellar research career. Jamie and his team have unlocked fundamental aspects of how the immune system works, which have led to new insights into tackling autoimmune diseases and cancer. We are delighted that he has received this recognition for his research.”

Sir Adrian Smith, President of the Royal Society, said: “It is an honour to welcome so many outstanding researchers from around the world into the Fellowship of the Royal Society.

“Through their careers so far, these researchers have helped further our understanding of human disease, biodiversity loss and the origins of the universe. I am also pleased to see so many new Fellows working in areas likely to have a transformative impact on our society over this century, from new materials and energy technologies to synthetic biology and artificial intelligence. I look forward to seeing what great things they will achieve in the years ahead.”

Professor Rossjohn will attend a ceremony in London in July where he will give a presentation of his work, sign the Charter book and be formally admitted as a Fellow

Read more about Professor Rossjohn in Monash Lens.

Click here to learn more about the Royal Society and see the full list of 2022 Royal Society Fellows.

Original article

Also published here.

See also: Cardiff university news, ARC Highlight.

The interplay between diet, the microbiota and immunity

Research in mice shows how diet alters immune system function through a gut microbe

At a glance:

  • Research in mice demonstrates how diet alters a gut microbe molecule that in turn prompts immune cells to downregulate inflammation
  • Study illustrates the molecular mechanism behind the longstanding view that diet, microbiota and immunity influence each other in myriad ways
  • Following more testing, findings could inform the design of small-molecule drugs that regulate immune response to treat inflammatory conditions

An international team of researchers including Monash University have found molecular proof of how diet ultimately affects immunity through the gut microbiome.

The team’s work, conducted in mice, have pinpointed a microbial molecule called B. fragilis that sets off an immune-signalling cascade triggered by the host’s diet of a metabolic breakdown of branch-chained amino acids in the mouse gut.

The multistep pathway begins with B. fragilis taking up the branch-chained amino acids and then converting them by a specific enzyme into sugar-lipid molecules that also have branched chains that are then spotted and picked up by a class of immune-signalling cells known as antigen-presenting cells, which in turn induce natural killer T (NKT) cells to exercise their immunoregulatory response through upregulating inflammation-controlling genes and immune-regulatory chemicals.

Furthermore, the team found that B. fragilis alters the structure of the sugar-lipid molecules that it metabolizes and renders them better capable of binding to receptors on specific immune cells and initiating a signalling cascade that culminates in downregulating inflammation.

The findings, published November 10 in Nature, offer a unifying explanation for the complex interplay between diet, gut microbiota and immune function. They are the result of collaboration among scientists at Harvard Medical School, Brigham and Women’s Hospital, Seoul National University, and Monash University in Australia.

NKT cells line the human gastrointestinal tract, the lungs and are also found in the liver and spleen and likely play a significant role in immune regulation and are implicated in a range of inflammatory conditions including ulcerative colitis, and to a possible role in airway inflammatory conditions, such as asthma.

While scientists have surmised for a long time that diet plays a role in immune health, the new study elucidates the precise molecular cascade behind diet and immune health, said study senior author Dennis Kasper, professor of immunology at Harvard Medical School.

“We have shown how diet affects the immune system through a microbe mediator in the gut, and this is a really striking example of the diet-microbiota-immunity triad at play,” Kasper said. “What this work really does is provide a step-by-step pathway from beginning to end that explains how and why this triad works and how diet ultimately affects the immune system.”

Using a structural biology approach, Professor Jamie Rossjohn, ARC Laureate Fellow at the Monash Biomedicine Discovery Institute, elucidated how the lipid structure engages with and binds to antigen-presenting cells—the immune cells that give NKT cells the go-ahead to produce anti-inflammatory chemicals.

“This work offers a great example of trans-disciplinary discovery-based research aimed at answering a major question in biomedical sciences, namely how the immune system can be modulated by the interplay between diet and the microbiota,” Professor Rossjohn said.

Study coinvestigator Seung Bum Park, professor of chemistry at Seoul National University, synthesized and the Harvard team tested 23 different configurations of the microbe-made immunomodulatory molecule to determine how each one interacts with the immune cells that regulate inflammation.

“Our new work demonstrates that the branching of the lipid structure induces a very different response—the branching in the structure induces an anti-inflammatory rather than a proinflammatory response,” Professor Kasper said.

The findings offer the hope that inflammatory diseases mediated by these NKT cells could one day be treated with inflammation-dampening microbial molecules made in the lab, the researchers said.

Co-authors included Sungwhan F. Oh, T. Praveena, Heebum Song, Ji-Sun Yoo, Da-Jung Jung, Deniz Erturk-Hasdemir1, Yoon Soo Hwang, ChangWon Lee, Jérôme Le Nours, Hyunsoo Kim, Jesang Lee, and Richard Blumberg.

Read the full paper (view only)  via SharedIt in Nature titled: Host immunomodulatory lipids created by symbionts from dietary amino acids. 

Original article