Revealed: our cellular guardians

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Everyone has a unique identity and awareness of ‘self’ – and this identity has a biological counterpart at the cellular level. This cellular ‘awareness’ is mediated by genes in the human leukocyte antigen (HLA) family, and these genes are the reason, for example, that transplanted organs are rejected unless efforts are made to match HLA types between donor and host.

HLA genes are the ones that vary the most between individuals, and they tag the surface of every cell in our body in a way that denotes precisely who and what we are as biologically individual.

There is, however, another side to these molecules, and it’s been an aspect that has baffled immunologists for decades.

Monash University researcher and Monash Health clinician Professor Richard Kitching explains that, normally, the immune system is trained to not attack ‘self’. Occasionally, this immune ‘tolerance’ breaks down and the result is a painful, life-changing or life-threatening autoimmune disease in which the immune system attacks and damages healthy tissue.

What has baffled immunologists, he says, is that certain HLA gene variants dramatically increase the risk of developing a particular autoimmune disease, while other HLA variants provide impressive levels of protection.

Now, Professor Kitching can explain the HLA effect on disease susceptibility with respect to Goodpasture disease – which was used as the research model – in which the patient’s immune system impairs kidney and lung function.

Even more importantly, the experimental systems developed during this research now provide an opportunity to develop better, cell-based therapies to protect against immune kidney diseases. The findings can also be used to test whether the new cell-based approach is applicable to other autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, Crohn’s disease and multiple sclerosis, he says.

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Sweet success for A/Prof Stephanie Gras

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Monash University’s Biomedicine Discovery Institute researcher Associate Professor Stephanie Gras has been honoured with a Georgina Sweet Award for Women in Quantitative Biomedical Science for excellence in the field.

Group leader and Monash Senior Research Fellow in the Department of Biochemistry and Molecular Biology, she was one of three women who won the award, which has a prize of $25,000.

“It’s a great recognition of my career so far and my work in biomedical research, particularly because the award application is reviewed by peers,” Associate Professor Gras said.

“It’s also great to have the opportunity to lead the way for women in science and make sure we can inspire young women to enter science as a career,” she said.

Associate Professor Gras, who is investigating how the immune system can be boosted to counter viruses including influenza and HIV, has several women in her team and plans to use part of the award to ensure they go to conferences next year.

“It gives me the opportunity to snowball the award to make my contribution to supporting women in science,” she said.

 

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Jamie Rossjohn elected into the Fellowship of the Australian Academy of Health and Medical Sciences

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Monash University researcher Professor Jamie Rossjohn has been formally inducted into the Fellowship of the Australian Academy of Health and Medical Sciences (AAHMS).

Being elected as a Fellow honours the important contribution Professor Rossjohn has made to health and medical research in Australia. Professor Rossjohn, ARC Laureate Fellow, is recognised internationally for being at the cutting-edge of advances in the field of immunology.

“On behalf of my team and I, I am delighted to receive recognition of my findings on immunity – research that has been conducted at Monash over the last 15 years.  I would like to take this opportunity to acknowledge and highlight the tireless work of the research assistants in my laboratory, key members of the team whose work underpins our endeavours,” Professor Rossjohn said.

 

More details about AAHMS elected fellows

Prima Biomed and Monash University receive funding grant for LAG-3 research project

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SYDNEY, AUSTRALIA – Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) (“Prima” or the “Company”) announces that the Australian Research Council (ARC) has awarded Prima and research partner Monash University a A$360,000 grant under its Linkage Project scheme to help fund a research project into the role of LAG-3 in immune responses.

In collaboration with Prima, Monash University’s Biomedicine Discovery Institute (BDI) Chief Investigator, Professor Jamie Rossjohn will conduct the study titled ‘Investigating the structure of a T cell immune checkpoint molecule’. It will assess T cell receptors and their role in the immune system and provide insights into the LAG-3 function and how it controls T cell signalling. The study could ultimately lead to the development of new innovative T cell immunomodulatory agents. ARC Laureate Fellow and Head of the Infection and Immunity Program at the Monash BDI, Professor Jamie Rossjohn, said: “This funding shows huge support for immunotherapeutics. Our proposal is innovative in combining state-of-the-art technology that will be fully integrated with the ground breaking work of Dr Triebel, the leading authority in LAG-3 biology. This will help us to further understand the way that LAG-3 controls T cell signalling, which is important for both cancer and autoimmunity.”

Prima’s Chief Scientific and Medical Officer, Dr Frederic Triebel, also welcomed the grant and said: “Working alongside one of the leading international groups in structural immunology, we are seeking to determine for the first time how LAG-3 binds with MHC class II and how this interaction is disrupted by the blocking antibodies presently tested as immune checkpoint inhibitors for cancer patients in clinical trials.”

The study will be conducted over a three year period. Professor Rossjohn will have overall oversight of the project and will be responsible for resources management of the grant. As the leading authority on LAG-3, Dr Triebel will provide his expertise and facilitate access to relevant LAG-3 specific constructs, reagents, mAb directed against LAG-3. Prima will also make a small additional cash contribution towards the study and provide staff and materials.

Image credit: Prima Biomed

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Turning back the tide of Rheumatoid Arthritis

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Evolutionary changes in genes linked to rheumatoid arthritis (RA) may be responsible for higher incidence and earlier onset in Indigenous North American populations.

An international team of scientists, co-led by Monash Biomedicine Discovery Institute(BDI) and University of Queensland researchers, embarked on research to look at why RA is more prevalent and severe in Indigenous populations.

Monash BDI’s Professor Jamie Rossjohn, together with UQ Diamantina Institute’s Professor Ranjeny Thomas, Leiden University’s (Netherlands) Professor Rene’ E Toes and University of Manitoba’s (Canada) Professor Hani El-Gabalawy, co-led the research which investigated how cells which keep the immune system specific become particularly cross-reactive in Indigenous North Americans with RA

“We found specific HLA genes were responsible for higher risk RA in Indigenous North Americans” Professor Thomas said.

“By using the amazing capabilities of the Australian synchrotron and the BDI, we were able to dissect the molecular basis for the increased prevalence of RA in native Americans” said Professor Rossjohn, ARC Laureate Fellow and Head of the Infection and Immunity Program at the Monash BDI.

HLA genes are used by the body to educate a person’s immune system to control infection, but in people with Rheumatoid Arthritis the process becomes confused, leading to an attack on the body’s tissues.

Professor Thomas said infection-fighting immune cells become more likely to cross-react with tissue cells as people aged.

“Indigenous North Americans and Indigenous Australians share increased susceptibility and complications to some viral infections, such as influenza,” she said.

“We are now interested to determine whether the same high RA susceptibility exists in Indigenous Australians as in Indigenous North Americans,” Professor Thomas said.

She said immune cells responding to HLA genes in North Indigenous Americans were particularly cross-reactive, resulting in RA being more prevalent and with earlier onset.

“Understanding the genes and how they contribute to the cause of RA in the Indigenous North American population means that specific immunotherapies could be designed for this population in the future,” she said.

She said because RA was under-researched in both urban and remote Aboriginal populations, researchers were planning to undertake similar work to understand prevalence, severity, HLA genes and the relevant infectious responses in Indigenous Australians.

The research was published today in the Annals of the Rheumatic Diseases.

 

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