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Discovery of a third T cell lineage

The immune systems of all vertebrates contain specialized cells, called T cells, that play a fundamental role in protecting against fungal, bacterial, parasitic and viral infections. T cells use ‘molecular sensors’ called T cell receptors (TCRs) on their surface that can detect and eliminate the invading pathogens. For most of the past four decades, it was considered that there were only two T cell lineages, αβ and γδ T cells, characterized by their cell surface expressed αβ and γδ TCRs, respectively.

In a paper published today in Science, an international team of scientists at the University of New Mexico (US), Monash University (Australia), and the US National Institutes of Health, has defined a novel T cell lineage, called γµ T cells, found only in marsupials (e.g. kangaroos and opossums) and monotremes (e.g. duckbill platypus).

Evidence for the γμ TCR came with the discovery of genes encoding the TCRμ protein whilst analyzing the first complete marsupial genome, that of the South American opossum Monodelphis domestica.  Oddly, distinct from conventional αβ and γδ TCRs, TCRμ was predicted to share similarity with the antibodies.

Using the Australian Synchrotron, the scientists at Monash University obtained a detailed three-dimensional image of the opossum γµTCR architecture that was unique and distinct from αβ or γδ TCRs. Noteworthy was the presence of an additional single antibody-like segment called Vμ domain with an architecture resembling to nanobodies, a unique type of antibodies. This discovery raises the possibility that γμ T cells recognize pathogens using novel mechanisms, distinct from conventional T cells.

“The discovery of a nanobody like structure in the γμ TCR has the potential to expand the immunology ‘toolbox’. Indeed, nanobodies discovered in the camel family (e.g. alpacas) have recently attracted considerable interests for their development as research and diagnostic tools and more importantly as immunotherapeutics in humans to combat cancer and viral infections such as COVID-19. Marsupials may offer an alternative source of nanobodies, one that is smaller, easier and cheaper to maintain than llamas or alpacas.” said Monash University Dr Marcin Wegrecki from the Biomedicine Discovery Institute, co-first author on the paper.

“Our findings further illustrate the value of exploring the world’s biodiversity for novelty beyond the standard animal research models, such as laboratory mice. Modern genomic tools applied to many species have opened the door to the myriad of immunological solutions to fighting pathogens that evolution has produced.” said Prof Robert Miller from the University of New Mexico, co-lead author on the paper.

“Many in-roads have been made in understanding the immune systems of humans and mice leading to the development of novel immunotherapeutic approaches enabling humans to combat highly pathogenic viruses. However, much less is understood on how immunity operates in other species that, in some cases, have been decimated by wildlife diseases. Ultimately our work may guide the development of veterinary approaches (e.g. novel vaccines) that will contribute to wildlife conservation.” said Dr Jérôme Le Nours from Monash Biomedicine Discovery Institute, co-lead author on the paper.

“This is a prime example of curiosity driven science leading to unexpected and transformative findings.” Le Nours stated.

The research findings were a culmination of a 12-year project that involved a multidisciplinary collaborative effort and the support from the ARC Centre of Excellence in Advanced Molecular Imaging, and funding from the US National Science Foundation, the US National Institutes of Health and the Australian Research Council.

Read the full paper in Science titled: The molecular assembly of the marsupial γμ T cell receptor defines a third T cell lineage.
DOI: 10.1126/science.abe7070

Original article

Congratulations Erica – Finalist of the Falling Walls Science Breakthroughs of the Year – Science in the Arts

The Falling Walls Science Breakthroughs of the Year ( 1-10 November) will highlight breakthrough thinking from around the world. Over the past months, they have received over 900 nominations from 111 countries.

They are delighted to introduce the finalists and present their science breakthroughs of the year in these ten categories: Life Sciences, Physical Sciences, Engineering & Technology, Social Sciences and Humanities, Science in the Arts, Digital Education, Science and Innovation Management, Emerging Talents, Science Start-Ups, Science Engagement Initiatives.

Breaking the Wall of Disabled Access to Science – Erica Tandori (Artist in residence, Rossjohn lab, Monash university)

Lying at the intersection between art, science and blindness, Tandori’s exhibitions use interactive sculptures to engage and inspire audiences of all ages and abilities. Her breakthrough is making art and science exhibitions inclusive, accessible and available to everyone globally.

Tags: Artificial Intelligence, Discrimination, Diversity, Education, Science Communication

Watch Erica’s presentation of her breakthrough below:

Erica Tandori is a legally blind artist, researcher and academic. She explores the intersections of art, vision loss and science. Tandori’s PhD focused on capturing the entoptic effects of her retinal disease through art, conveying an ‘eye-witness’ account of blindness. As resident artist at the Rossjohn Lab, Monash University, Erica creates multi-sensory, multi-modal artworks communicating biomedical research to blind and low-vision audiences. This inspires people of all ages and abilities to learn, understand and appreciate the wonders of science.

 

Other Science in the arts finalists

Further information:

FALLING WALLS AND BERLIN SCIENCE WEEK, THE WORLD SCIENCE SUMMIT:

Falling Walls and Berlin Science Week invite you to this year’s World Science Summit, held remotely from 1 – 10 November 2020. This year we shift from physical events to a global virtual showcase, with free digital access for everyone. We acknowledge the combined effort of scientists worldwide to overcome the pandemic, and its many effects. Make sure to attend this event, where some of the world’s best researchers gather to discuss and celebrate the most recent breakthroughs in science and society from all over the world.

WHEN

1 – 10 November 2020, with a daily science highlight programme at Noon GMT (13.00 Berlin Time) and the Grand Finale on 9 November

WHAT

500+ speakers, 200+ sessions, 1 digital platform with live-streamed breakthroughs, expert panels, workshops and lectures

WHERE

Completely remote – Free digital access from wherever you are plus selected physical events in Berlin

Congratulations Rachel – Winner of the BDI Student Symposium 5 minute talk category

The annual BDI student symposium looked a bit different this year, with face-to-face being replaced with face-to-screen. Despite these changes, we were so happy to see such a huge turnout of students from across the BDI showcasing their research through talks and poster presentations.

Thank you to all the students and assessors who made the day run smoothly and congratulations again to our winners!

Student talks: Hot off the plate reader – be the first to hear about the exciting results our students are generating.

WinnerNicholas Choo 

Runner up: Bob Leung 

5-minute talks: With just five minutes, students will give you the highlights of what their research can achieve.

WinnerRachel Farquhar

Runner-upYusun Jeon 

Image: Rachel delivering her talk via zoom.

Posters: A chance to have a chat with our students about their exciting new data.

WinnerMariam Bafit

Runner-up: Kerry Mullan

The BDI Student Symposium was held on Friday, September 25th and showcased the work of BDI Graduate Students.

Adapted from Monash BDI Notices.

Unlocking Your Inner Eye. Artistic Intelligence with Erica Tandori, a Legally Blind Artist

Artist in residence, Dr Erica Tandori is expanding the frontiers of Artificial Intelligence (AI) and Art. Her work at Monash University in the Rossjohn lab focuses on communicating science through art for the visually impaired. She is now expanding this work and utilising robotics in her artistic creations to create a multi-sensory experience. AI and robotics have the potential to transform lives and promote social good. Harnessing these technologies to create art exhibitions exploring science and biomedicine is enabling greater inclusion, accessibility and education for low vision, blind and diverse audiences. Erica’s work and her personal story provide an impressive example of AI for social good, promoting diversity and inclusion in science and technology.

Art is not in the retina. It’s in the imagination. Hear the story of Erica Tandori, a visually impaired artist, who is using AI to create multi-sensory art experiences showcasing the wonders of biological life.

TOPICS DISCUSSED IN THIS EPISODE:
– Art is not in the retina, it’s in the imagination
– Natural intelligence
– Tapping into the soul to power AI and art
– Art for good
– Fostering wonderment to think differently

Panelists include Neil Sahota, World Wide Business Development Leader, IBM Watson and Michael Ashley, Screenwriting Professor at Chapman university

Original article

Novel immune-oncology approach for potential cancer treatment

A research collaboration between Monash University and Lava Therapeutics details a novel immune-oncology approach for the potential treatment of cancer. Instrumental to the study was co-first author Dr Roeland Lameris from Amsterdam UMC and colleagues from the University of Melbourne.

Published in Nature Cancer, the study, co-led by Monash Biomedicine Discovery Institute’s ARC Laureate Fellow Professor Jamie Rossjohn and Dr Adam Shahine,  highlights the synergy between an antibody fragment, known as a nanobody, that not only acts as a bridge helping to link together two key immune cell receptors but also takes advantage of their interaction, enabling the body to enhance its immune response to cancer.

These antibody fragments, denoted as nanobodies, act by targeting the interaction between a molecule known as CD1d and Natural Killer T cells (NKT) in a stable and long-lasting manner, against tumour samples of patients with multiple myeloma and acute myeloid leukemia.

The new findings will serve as a model for the potential generation of new and effective therapies against a broad range of cancers.

Using the Australian Synchrotron, the team at Monash University provided detailed atomic insight into how the nanobodies exerted their effect on immune cells in a cancer model. “We were able to precisely visualize how the nanobody simultaneously recognized CD1d and the NKT TCR, thereby providing a molecular basis for their anti-tumour properties” Professor Rossjohn stated.

Hans van der Vliet, professor in medical oncology at Amsterdam UMC and chief scientific officer of Lava Therapeutics says “By targeting and boosting natural immune cells that are inherent in all humans, such as NKT cells and gamma-delta T cells, for an enhanced therapeutic effect, we believe our approach could ultimately translate into a broadly applicable immunotherapeutic approach for a range of cancer indications.”

“This collaborative work paves the way for rationally developing improved therapeutics to treat a range of cancers” said co-first author Dr. Shahine.

Read the full paper in Nature Cancer titled: “A single domain bispecific antibody targeting CD1d and the NKT T cell receptor induces a potent anti-tumour response
DOI: 10.1038/s43018-020-00111-6

Original paper

Front cover image

Image: Nanobodies targeting of a tumour cell.

Image Credit: Erica Tandori