Congrats Camilla on your co-1st author Cell paper

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Ancient gene offers new clue to disease susceptibility for First Nations people

A world-first discovery has identified a previously unknown gene variant influencing first-line immune defences in First Nations people – who are at higher risk of severe respiratory viral diseases – and offers insights for improved disease prevention strategies.

An international team of researchers, co-led by Monash University and the Peter Doherty Institute for Infection and Immunity (Doherty Institute), has gained new understanding of the immunity of First Nations people across Oceania, which includes Australasia, Melanesia, Micronesia and Polynesia.

Published in Cell today, the eight-year project was the first of its kind to comprehensively map a component of the first line immune defences, termed natural killer cells, in Oceania’s First Nations populations, including First Nations Australians.

Natural killer cells are part of the body’s first line of defence against pathogens, which can restrict viruses from replicating in the earliest stages of infection. This is crucial because they can either eliminate low level infection completely or buy time for the generation of virus-specific immunity. Consequently, these immune cells play a key role in an individual’s ability to both prevent infection and recover from a virus.

First Nations people globally, including Aboriginal and Torres Strait Islander people, are at high risk of severe respiratory viral diseases, including COVID-19, pandemic influenza and seasonal influenza. In addition to social determinants of health, genetic variations within immune cells may contribute to the increased risk.

In partnership with Menzies School of Health Research (Northern Territory), the University of Colorado and Stanford University, the researchers evaluated natural killer cells in First Nations people, conducting in-depth genomic and molecular analyses at the Stanford University genomic facility and the Australian Synchrotron.

Dr Camilla Faoro, co-first author of the study from Monash University’s Biomedicine Discovery Institute, used the Australian Synchrotron to provide detailed structural insights into the impact of killer cell immunoglobulin-like receptors found in First Nations Peoples at the molecular level.

“We have shown how the Indigenous and Māori forms of KIR3DL1 interact with the most common HLA molecules in Oceania, which explains why they bind more tightly than the KIR3DL1 forms predominant in other parts of the world,” Dr Faoro said. “This tighter binding changes the capacity of natural killer cells to sense and respond to infection.”

Monash BDI’s Dr Camilla Faoro, co-first author on the Cell publication.

Monash BDI’s Dr Camilla Faoro, co-first author on the Cell publication.

The University of Melbourne’s Professor Katherine Kedzierska, Head of the Human T Cell Laboratory at the Doherty Institute and co-senior author of the paper, has been co-leading the research since 2016.

“Natural killer cells, a type of white blood cell, are key in mediating early immune control against a broad range of viruses,” Professor Kedzierska said. “We focused our research on the origin, distribution and functions of killer cell immunoglobulin-like receptors in First Nations people, as these receptors are crucial components that direct immune responses following viral infections.”

Specifically, the study examined a highly variable natural killer cell receptor, called KIR3DL1, of which there are over 200 forms in humans, capable of binding to subsets of a person’s human leukocyte antigens (HLA) molecules, which present viral peptides for recognition by immune cells, and are themselves highly variable.

Professor Kedzierska said that, critically, the team identified an ancient variant of the natural killer receptor that appears to be exclusive to the people of Oceania, binding more strongly to the HLA variants that are common to Oceanic peoples.

“Our analyses of over 1,300 individuals revealed that the frequency of this Oceanic variant was as high as 28 per cent among highland Papuans and around six per cent in First Nations people from Northern Australia, which could influence susceptibility to infection,” she said.

She noted that genetic and immunological studies often do not involve First Nations and other minority populations around the world.

“Recent studies including this one, underscore the importance of inclusively working with First Nations peoples. Our learnings may inform the design of new vaccines or vaccine regimens and immunotherapies, helping to ensure these agents are effective for the broad sweep of human populations,” she said.

The University of Melbourne’s Professor Andrew Brooks, Head of the Natural Killer Cell Laboratory at the Doherty Institute and a co-senior author of the paper, said the extent to which natural killer cells can respond to viral infections and cancer is dictated by these genes, which are among the most variable in the human genome.

“At a global level, genetic differences contribute to population-specific immune variation, so gaining insights into these differences is important for both addressing and reducing disparities in health outcomes,” Professor Brooks said.

“An understanding of this diversity is key not only to explain why responses to viral infections differ from person to person, but it may also allow us to identify individuals and/or populations at higher risk of severe disease.”

Additional information:

  • Peer review: Norman, PJ, et al. An archaic HLA class I receptor allele diversifies natural-killer-cell-driven immunity in First Nations peoples of Oceania. Cell (2024). DOI: 10.1016/j.cell.2024.10.005
  • Funding: This study was supported by the Australian Research Council and NHMRC.
  • Collaboration: This study was led by Katherine Kedzierska, Steven Tong, Andrew Brooks, Jamie Rossjohn and Paul Norman, in collaboration with Monash University, Menzies School of Health Research, University of Colorado and Stanford University.

Original article

Media contacts

Cheryl Critchley
Media and Communications Manager, Monash University
P +61 (0) 477 571 442
E cheryl.critchley@monash.edu

Aline Riche
Senior Communications and Media Officer, Doherty Institute
P +61 (0) 403 204 336
E Doherty-media@unimelb.edu.au

Come visit us at the Coeliac Australia Gluten-free Expo

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Coeliac Australia is excited to announce that the Coeliac Australia Gluten-Free Expo is back in Melbourne in 2024!  October 5 and 6

​​Don’t miss Australia’s largest 100% Gluten-Free Event in Victoria!  It’s a fantastic opportunity to learn, taste, and shop the latest in gluten-free food.  With many exhibitors offering show specials, attendees can grab a bargain while discovering new and delicious options. You don’t want to miss this exciting event!

What’s on

Come find us at the Rossjohn lab – Monash Sensory Science stand.

We are delighted to be part of the Coeliac Australia’s Gluten-Free Expo! We are autoimmune disease researchers, especially coeliac disease. We have created artworks, tactile models, and multisensory science books containing audio visualisation of cellular activity for blind, low vision and diverse communities. Come and see us at the Health Hub where you’ll be guided through a tactile journey from gluten to the development and pathology of coeliac disease.

Gluten is more than just an allergy! Join us to explore how gluten triggers a pro-inflammatory immune response and its impact on patient health and quality of life

Education Stage

Gain valuable insights on managing a gluten-free diet and the latest research in coeliac disease.

Fun for the Kids

Enjoy activities designed for our younger attendees.

Sample, Taste, and Shop

Discover a fantastic lineup of exhibitors and food vendors ready to tantalise your taste buds.

For more information visit here.

Buy tickets here.

Congrats Ben and team on your Nature paper

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Structure of a key “trigger” of the immune response solved

An international collaboration, involving researchers from Monash University and the University of Oxford, has led to a breakthrough in our understanding of how immune responses are started. The study has just been published in Nature.

The human immune system comprises multiple important white blood cells (i.e., lymphocytes) including B cells and T cells that fight off infections and cancers. Basic discoveries leading to an understanding of how lymphocytes function have led to the development of immunotherapies and vaccines.

There are two types of T cells in humans, called αβ T-cells and γδ T cells, each of which expresses on their surfaces either an αβ T cell receptor (TCR) or a γδ TCR, respectively. In 1957, Frank Macfarlane Burnet, a famous Australian immunologist, predicted the existence of these receptors and speculated that they would “trigger” clonal lymphocyte expansions, producing enough cells to fight off infections. We now recognize that TCRs have the pivotal role of recognising molecules derived from foreign pathogens or tumours. While less is known about γδ T cells than αβ T cells, they are emerging as key players in immune defence and are becoming increasingly important for immunotherapy.

Figure. The image shows the unusual, flexible arrangement of the γδ TCR versus the αβ TCR. B-cell receptor is expressed by antibody-making B-cells.

The team determined the molecular structure of the TCR found on the surface of γδ T cells using cryogenic electron microscopy. This technically demanding project took over a decade from conception to completion and was made possible by the expertise within the Monash Ramaciotti Centre for Cryo-Electron Microscopy.

The new structure unexpectedly showed that the γδ TCR is remarkably flexible, in stark contrast to relatively rigid αβ TCRs. The work also showed that the γδ TCR is very likely the more primeval receptor and completes the initial structural analysis of Burnet’s “trigger” receptors, alongside companion paper also published in Nature.

“This flexibility is key to the ability of the γδ TCR receptor to recognise a wide array of binding partners, which underscores the unique role it plays in the human immune system”, Dr Benjamin Gully of the Monash Biomedicine Discovery Institute, co-first author of the study stated.

According to Professor Simon Davis, from Oxford University and joint senior author of the study, γδ T-cells are becoming increasingly important therapeutically.

“The new structure helps constrain theories of how TCRs trigger lymphocytes, and should be helpful, especially, for re-engineering TCRs and optimising their use in the clinic” he said.

The authors would like to acknowledge support from the Australian Research Council Discovery Program which made this basic research project possible.

Read the full paper in Nature: Structure of a fully assembled γδ T-cell antigen receptor.

DOI: 10.1038/s41586-024-07920-0

Some of the Monash University co-authors on the Nature publication (left to right): Liam Rashleigh, Michael Rice, Dr Benjamin Gully, Dilshan Gunasinghe, Professor Jamie Rossjohn, Hari Venugopal.

 

Original article

Monash Sensory Science exhibition and books gain international recognition

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A creative and inclusive Monash University program to employ laboratory staff with disabilities and bring science to life for those with low vision has been highlighted in the journal Cell .

It is hoped that this publication will catalyse other researchers and institutions to be more inclusive in the workplace and in public engagement.

Monash Sensory Science began as a Monash Biomedicine Discovery Institute (BDI) internship program for people with disabilities and a one-off exhibition for blind and low-vision communities.

Supported by the ARC and Monash University, it has evolved into a national and international multisensory, accessible science initiative involving accessible employment, exhibitions and books championing inclusion in science communication.

The founder of this initiative and BDI researcher Professor Jamie Rossjohn reflected on the opportunities he’d received during his career and whether he would have had them if he had a disability.

“The answer to this question is likely no, because all too often, science is taught and communicated through the lens of able-bodied people to the exclusion of people with disabilities,” Professor Rossjohn said in the article .

“There was also the realisation that in the two decades of running a lab, we hadn’t included employees with diverse physical needs. People with disabilities face huge challenges in securing employment, and I realised that we are part of the problem.”

After contacting disability-focused employment agencies, Professor Rossjohn found some job seekers were prepared to work voluntarily as it was so rare to gain lab experience.

He designed an internship program around inclusion and equality, working with service providers to understand interns’ goals, and the university’s human resources requirements.

The program began in 2017 with three-month paid positions in administrative and technical lab roles. Wise Employment helped with adjustments such as assistive technologies, sign language interpreters and staff disability awareness training.

“One researcher is now undertaking a master’s of biomedical and health science at Monash, while another intern, concerned they couldn’t perform particular types of lab work, pivoted instead to computational biology and is now completing a PhD in genetics at our university,” Professor Rossjohn said.

A notable success story is Dr Erica Tandori, a legally blind artist who joined the team in 2018 via Vision Australia after completing a PhD.

Dr Tandori became legally blind at 23, due to a genetic condition called juvenile macular degeneration, and returned to university after raising her children to conduct art-based research. Among other things, she used oil paint and drawing to show what her condition looked like from a patient’s perspective.

At the BDI, Dr Tandori developed a tactile exhibition to bring the microscopic world of cells and microbes alive for the blind and vision impaired. She worked with lab scientists and others across the BDI to create large tactile posters with braille labels and large text, 3D models of immune cells, viruses, and proteins, and braille-inspired amino acid sculptures and handcrafted models.

The first Monash Sensory Science exhibition was held in 2018, and it has since incorporated an internship program for people with disabilities. “Most of all, I realised art has enormous potential in research and in communicating science and medicine,” Dr Tandori told Cell.

“I began using food, paper clay, and found objects to make sculptures of proteins, cells, viruses, and bacteria, articulating their surfaces with couscous, pasta, rice, seeds, leaves, clay, paper and other items. Trying to invoke connections and memories of familiar things when touched, I was instinctively beginning to develop a multisensory language that could assist blind and low-vision people to grasp more complex concepts in non-visual ways.”

More exhibitions followed, and multisensory, interactive science ‘exhibitions in a book’ for blind, low-vision and diverse-needs readers were developed with the help of Dr Stuart Favilla and Dr James Marshall from Swinburne University of Technology.

“We have also staged virtual exhibitions internationally and brought numerous small-scale outreach exhibitions to blind and low-vision people in community settings,” Dr Tandori said. “This has been a shared vision with my supervisor Jamie, a recognition we both have that science and immunology affect everyone and should be accessible to all.”

Adds Professor Rossjohn: “Witnessing the positive experiences of our interns has been heartwarming and immensely rewarding, and there is a recognition that the key to success lies in opportunities afforded to us in life.

“We hope our experiences can motivate other research labs and institutions to develop more inclusive workplaces, opportunities and educational programs for people with disability. This is where philanthropy could play a role in supporting such initiatives. The benefits are not a one-way street – diversity brings a richer, more tolerant and rewarding research environment and culture to all.”

Read the full paper in Cell, Advancing accessible science for low-vision and diverse-needs communities.

DOI: 10.1016/j.cell.2024.05.020

Original article

Professor Jamie Rossjohn honoured with prestigious international award

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Leading researcher Professor Jamie Rossjohn from the Monash Biomedicine Discovery Institute has been selected to receive the Ceppellini Award 2024 in memory of Ruggero Ceppellini, one of the pioneers in the field of immunogenetics. The prestigious lifetime achievement award was presented at the 37th EFI Conference in Geneva, Switzerland on 20 May 2024.

As the awardee, Professor Rossjohn was also invited to present his work in the form of the Ceppellini Lecture during the conference’s opening ceremony. His lecture was on the topic of T cell immunity, specifically interactions mediated by the T cell receptor.

Professor Rossjohn received the Ceppellini Award for his significant contribution to understanding defined events central to cellular immunity. His research in T cell immunity has provided an understanding of the molecular basis of peptide, lipid and small molecule presentation – both in the context of infectious disease and unwanted immunity, as occurs in autoimmune disorders such as rheumatoid arthritis and in drug and food hypersensitivities such as Celiac Disease. Professor Rossjohn is the 35th recipient of the award, which he accepted from Dr. Ann-Margaret Little, President of the European Federation for Immunogenetics.

Professor Jamie Rossjohn receiving the Ceppellini award

Professor Jamie Rossjohn receiving the Ceppellini award

Professor Rossjohn is currently a National Health and Medical Research (NHMRC) Investigator Fellow at Monash University, was a recent Australian Research Council Laureate Fellow from 2017-21 and has been recognised as a Clarivate Web of Science Highly Cited Researcher from 2018-2023.  In 2022, Jamie was elected as a Fellow of the Royal Society (UK), a Fellow of the Australian Academy of Health and Medical Sciences in 2017 and a Fellow of the Australian Academy of Science in 2014.

Professor Rossjohn said that it was an honour to receive the Ceppellini Award.  “It came as a bit of a shock to me, and my close companion, Ziggy, to be recognised in this manner, as some very heavy hitters have come before me in receiving the Ceppellini Award, “ he said. “It’s a testament to our sustained research in this area for the last 20-plus years, and of the collaborations, research fellows and students who have worked alongside me. These findings would not have been possible without funding from the NHMRC and ARC, and most importantly, the  ‘think big’ research environment that Monash fosters.”

Find out more about Professor Jamie Rossjohn’s research.

Original article