Jamie receives 2018 ASBMB Lemberg Medal

Monash Biomedicine Discovery Institute (BDI) congratulates Professor Jamie Rossjohn FAA FAHMS FLSW FMedSci, Head of the Infection and Immunity Program, who is the 2018 Australian Society for Biochemistry and Molecular Biology (ASBMB) Lemberg Medal recipient.

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 recipient, click here.

For a list of the previous Lemberg Medal recipients, click here.

Original article

New compound helps activate cancer-fighting T cells

Invariant natural killer T (iNKT) cells are powerful weapons our body’s immune systems count on to fight infection and combat diseases like cancer, multiple sclerosis, and lupus. Finding ways to spark these potent cells into action could lead to more effective cancer treatments and vaccines.

While several chemical compounds have shown promise stimulating iNKT cells in animal models, their ability to activate human iNKT cells has been limited.

An international team of top immunologists, structural biologists, and chemists published in Cell Chemical Biology the creation of a new compound that appears to have the properties researchers have been looking for. The research was co-led by Monash Biomedicine Discovery Institute’s (BDI) Dr Jérôme Le Nours, University of Connecticut’s Professor Amy Howell and Albert Einstein College of Medicine’s Dr Steve Porcelli.

The compound – a modified version of an earlier synthesized ligand – is highly effective in activating human iNKT cells. It is also selective – encouraging iNKT cells to release a specific set of proteins known as Th1 cytokines, which stimulate anti-tumour immunity.

One of the limitations of earlier compounds was their tendency to cause iNKT cells to release a rush of different cytokines. Some of the cytokines turned the body’s immune response on, while others turned it off. The conflicting cytokine activity hampered the compounds’ effectiveness.

The new compound – called AH10-7 – is uniquely structured so that does not happen.

“One of the goals in this field has been to identify compounds that elicit a more biased or selective response from iNKT cells, and we were able to incorporate features in AH10-7 that did that,” Professor Howell said.

The robust study, years in the making, also applied advanced structural and 3D computer modelling analysis to identify the underlying basis for the new compound’s success. These highly detailed insights into what is happening at the molecular level open up new paths for research and could lead to the development of even more effective compounds.

The molecular analysis helped validate and explain experimental results.

“By exposing a crystalized form of the molecular complex to a high-intensity X-ray beam at the Australian Synchrotron, we were able to obtain a detailed 3-D image of the molecular interplay between the invariant natural killer T cell receptor and AH10-7,” Dr Le Nours said.

“This enabled us to identify the structural factors responsible for AH10-7’s potency in activating iNKT cells. This valuable insight could lead to the development of even more effective anti-metastatic ligands,” he said.

In the current study, the research team made two significant modifications to an α-GalCer ligand in an attempt to make it more effective. They found that adding a hydrocinnamoyl ester on to the sugar stabilized the ligand and kept it close to the surface of the antigen-presenting cell, thereby enhancing its ability to dock with and stimulate human iNKT cells. In addition, trimming off part of the molecule’s sphingoid base appears to initiate the critical Th1 cytokine bias. Both changes, working in tandem, strengthened the effectiveness of the entire molecular complex in terms of activating human iNKT cells, Professor Howell says.

Original article