Discovery of a rare human gene mutation that causes MAIT cells to disappear

A collaboration between Monash Health, the Australian Genomics Health Alliance (AGHA) and researchers at the Monash Biomedicine Discovery Institute has led to the discovery of a rare single gene mutation in a patient that eliminates an immune cell population, namely MAIT cells.

This study’s journey began with a patient of Dr Samar Ojaimi from Monash Health who presented with a mild primary immunodeficiency with no known cause. He was identified as a candidate for the Genetic Immunology Flagship of AGHA led by Professor Matthew Cook from the Centre for Personalised Immunology at the Australian National University, which focuses on identifying genetic causes for immunological diseases.

The genome sequencing by the AGHA team identified a rare mutation in the gene encoding a protein called MR1, which normally helps initiate an inflammatory response from an immune cell population called mucosal-associated invariant T (MAIT) cells.  However, upon further investigation by a research team from Monash BDI, led by Dr Lauren Howson, they uncovered there had been a complete loss of this immune cell population, while the rest of the immune system remained intact.

“We studied the patient’s MR1 protein structure and found that the mutation prevented MR1 from being able to bind the vitamin metabolite it normally presents in order to activate MAIT cells. This led us to look at the patient’s immune system to see what effect the mutation had on the MAIT cell population and we were surprised to find it completely gone,” Dr Howson said.

A man gazes at the complex protein structures of his own immune system, and the rare genetic mutations that caused his illness, leading scientists to a dramatic discovery. Image © Dr Erica Tandori

Published in Science Immunology, the study demonstrates the power of interdisciplinary collaboration to uncover the impact of a single gene mutation and aid in diagnosis of rare immune disorders.

It not only advances the MR1 and MAIT cell biology research fields, but also demonstrates the substantial impact that discovery-based research can have when combined with clinical and genetic research, creating an avenue for advanced personalised medicine for rare genetic and immune disorders.

“This occurrence of a single immune cell population loss in a person gives us invaluable insight into the important role that this cell type plays in human immune responses,” Dr Howson said.

Professor Cook said: “Human genomics is a powerful method for advancing our understanding of the complexity of immunity.

“Genome sequencing has emerged as a crucial tool for both diagnosis and discovery of immune-mediated disease.”

Image: A man gazes at the complex protein structures of his own immune system, and the rare genetic mutations that caused his illness, leading scientists to a dramatic discovery. Artwork by Dr Erica Tandori.

Read the paper titled: “Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1” Science Immunology.

Original article

Congratulations to Rachel: Faculty Three minute thesis (3MT) 2020 finalist

An 80,000 word PhD thesis would take 9 hours to present. Their time limit… 3 minutes

Watch our PhD student, Rachel Farquhar’s 3 minute PhD thesis video:

Competitors were not judged on video/ recording quality or editing capabilities. Judging focused on the presentation, ability to communicate research to a non-specialist audience, and 3MT PowerPoint slide.


The Three Minute Thesis (3MT®) is an academic research communication competition developed by The University of Queensland, and celebrates the exciting research conducted by PhD students in Australia and around the world.

Call for immunology to return to the wild

A multidisciplinary research team from more than 10 universities and research institutes has outlined how integrating a more diverse set of species and environments could enhance the biomedical research cycle.

The viruses that cause COVID-19, AIDS, Ebola, and rabies – among others – all made the lethal jump from wildlife into humans.

In an article published in Science, the researchers argue that understanding how the immune system works in animals that live with coronaviruses in a natural environment, such as bats, can give us direction for developing treatments and vaccines to protect humans from viruses.

Lead author Dr Andrew Flies from the Menzies Institute for Medical Research at the University of Tasmania, says this is not a new concept.

“The very first vaccine arose from observing people interacting with animals in a real-world environment. Specifically, milkmaids who acquired a mild cowpox infection from cows were protected from the deadly smallpox. That observation led to the idea of inoculating people with non-lethal viruses to protect them from deadly viruses. This type of discovery can only be made by studying new species in variable environments.”

Modern research relies heavily on mouse experiments in laboratory settings, which limits the scope for this type of ground-breaking discovery.

An example of a long-term payoff from stepping out of the lab is the discovery of a new class of antibodies, often referred to as nanobodies, in camels. Easier and faster to make than traditional antibodies used in biomedicine, camel-derived nanobodies are playing an important role in biomedical research, including the global COVID-19 response.

“We are really excited to see how our initial group discussions held at the first Australian Wild and Comparative Immunology (WACI) workshop led to publishing a Perspective article in a world leading journal,” said co-author Dr Jérôme Le Nours, from the Biomedicine Discovery Institute at Monash University, who was co-organiser of the WACI meeting.

Associate Professor Anne Peters, Monash University, co-author and consortium collaborator, added: “There are many excellent wildlife and disease ecologists, veterinarian scientists and immunologists in Australia, and beyond. We hope that our contribution will inspire them to seek mutually beneficial, inter-disciplinary collaboration”.

WACI Consortium collaborator and co-author Associate Professor Julie Old from Western Sydney University said it’s important for immunology research to include more diverse species.

“If we want to evolve our understanding of the immune system, and potentially get ahead of any future pandemics, the research community needs to expand. We need to broaden our scope, and bring new species and new environments into the research paradigm.”

Associate Professor Michelle Power from Macquarie University said: ‘‘Realising wild immunology needs initiatives like the WACI Consortium that harness the wide expertise of scientists and diverse technologies within individual. The risks of emerging infectious diseases are not going away. We need new ideas, new tools and dynamic collaboration to address them”.

The Director of the Menzies Institute for Medical Research, Distinguished Professor Alison Venn, said new technology has broken down research barriers to integrating new species and environments into the research cycle.

“Proactive investment in wild immunology can stimulate discoveries with real-world applications for human and veterinary medicine and conservation. It could help us prepare for the next pandemic.”

Read the Rewilding immunology article published in Science.

Learn more about how integrating a more diverse set of species and environments could enhance the biomedical research cycle by watching the video below.

Original article