Jamie receives 2018 ASBMB Lemberg Medal

This prestigious medal honours Professor Rossjohn’s significant and sustained contributions to the understanding of the molecular basis underpinning immunity.

Awarded annually, the Lemberg Medal is presented in memory of Emeritus Professor M.R. Lemberg, who was the Society’s first President and Honorary Member. Only three other scientists from Monash University have won this Medal. Professor Rossjohn joins the esteemed company of Professor Anthony Linnane (1973), Emeritus Professor Phillip Nagley (2001) and the Dean of the Faculty of Medicine, Nursing and Health Sciences and Academic Vice-President, Professor Christina Mitchell (2015).

“An outstanding team of researchers who work alongside me, coupled with the continuous and strong support of Monash University, have enabled numerous exciting finds in the area of immunity to be made over the last 15 years,” Professor Rossjohn said

Since his relocation to Monash in 2002 to pursue a program of research centred on structural immunology, Professor Rossjohn has focused on defining the key molecular interactions underlying receptor recognition events that underpin immunity, both from the aspect of protective immune control and with regard to autoimmunity. Such findings were in close collaboration with leaders in the field, including Professor James McCluskey from the University of Melbourne.

For example, Professor Rossjohn, alongside Professor McCluskey and Professor David Fairlie, provided a structural basis of how vitamin B metabolites can be presented by MR1 and recognised by Mucosal-associated T-cells (MAIT cells), thereby revealing an entirely new class of antigen in immunity.

Professor Rossjohn’s research on the immune system, how the body reacts to infection and what happens when the immune system fails has led to a sustained advancement of knowledge in the field of immunity. His work has been generously supported by the Anti-Cancer Council, the NHMRC, and the ARC, including the current Centre of Excellence in Advanced Molecular Imaging.

As the recipient of the 2018 ASBMB Lemberg Medal, Professor Rossjohn will attend the ComBio2018 conference in September to give the Lemberg Medal Lecture.

For more information about the 2018 ASBMB Lemberg Medal, see https://www.asbmb.org.au/awards/jamie-rossjohn/

Original article

Could people living with coeliac disease one day be able to have their cake and eat it, too?

“If the stomach be irretentive of the food and if it pass through undigested and crude, and nothing ascends into the body, we call such persons coeliacs.”

Although coeliac disease is fairly common, affecting about one in 70 people of European descent, it’s still challenging to diagnose and treat. It’s best known for its classic digestive symptoms – diarrhoea and bloating — but it can also manifest in neurological conditions, skin rashes, osteoporosis, infertility and anaemia, or sometimes nothing at all. Children experience failure to thrive, delayed puberty, cognitive and behavioural issues and tooth enamel problems.

“It has such a broad spectrum of symptoms that some people don’t even know they have it,” says Dr Hugh Reid, who’s studying coeliac with his team in the Infection and Immunity group in Monash’s Biomedicine Discovery Institute. “Gastroenterologists think it’s very much underdiagnosed.”

Using the Australian Synchrotron facility, Dr Reid and his team look at how individual protein molecules behave when a coeliac patient ingests gluten. “It’s basically a train wreck.”

First off, gluten contains the amino acid proline. Enzymes in the gastrointestinal tract that break strings of amino acids into smaller fragments, or peptides, can’t chop up proline-heavy proteins very well. “Instead of peptides of just one to a few amino acids long, you can get up to 10 to 20 amino acids on that fragment,” says Reid.

Another thing all coeliac patients have in common is an increased amount of an enzyme called transglutinase 2 (TG2). It transforms one of these amino acids into a version that’s negatively charged, effectively making it “sticky”.

These sticky strings then bind to HLA molecules, specialised protein complexes embedded in the outer surface of our cells. They perform the critical task of scooping up protein fragments and presenting them to T-cells, the roving border patrol of the immune system.

If the receptors on the surface of a T-cell mesh with a peptide on an HLA molecule in just the right way, an alarm goes out and the troops are called in. This is how the immune system distinguishes self from non-self, harmless proteins in food from dangerous bits of bacteria. It’s a complicated system that works astonishingly well – most of the time.

Because there are so many possible combinations of the 20 amino acids, we produce many different HLA molecules to present peptides and many different specialised T-cells to recognise them. Coeliac patients have been dealt a rotten hand here – they have genes that produce one or two HLA versions with a particular affinity for these specific long, sticky strings of gluten residues.

Then, one of their T-cells mistakenly recognises this particular peptide presentation as being harmful, and unleashes a massive inflammatory response that damages the lining of the intestine and produces autoantibodies that can go on to attack other organ systems.

“The thing that makes this extraordinary is that this [peptide presentation] just happens to be the lock that this [T-cell receptor] key fits,” says Reid. “It’s just terribly bad luck.”

Original article