Congrats Adam on your Cell paper

Researchers create “Lipidomic Map,” offering insights into immunology

An international team of scientists has developed a method for simultaneously detecting thousands of lipid molecules that are displayed to T cells in the human immune system.

The study, co-led by Professor D. Branch Moody, MD, of the Division of Rheumatology, Immunity and Inflammation at Brigham and Women’s Hospital, and Adam Shahine, PhD, at the Monash Biomedicine Discovery Institute represents a collaboration among researchers from Oxford, United Kingdom, Monash University in Melbourne, Australia and Groningen, Netherlands. The results were published today in Cell.

The team developed a new and sensitive method to detect more than 2,000 lipids bound to CD1 antigen presenting molecules, which display antigens to the human immune system.

While scientists have long known that T cells recognise antigens, until the 1990s, it was thought that these antigens were always peptides derived from proteins. Because lipids are not encoded by genes and are instead made by enzymes and form into membranes, they have entirely different functions and positions in the cell.

The ability to measure many lipid antigens at one time will allow future researchers to cross-check any disease-related lipid of interest to the list of candidate lipid antigens from this map and potentially make connections to diseases.

Their efforts yielded the first integrated CD1 lipidomic map, which could help guide the investigation and discovery of lipid blockers and antigens for T cells and support the view that lipids normally influence immune responses.

The research builds on earlier methods that separate cellular lipids in one chromatographic system, which provided only a limited perspective. The new structural biology work, undertaken by Dr Shahine, ARC DECRA fellow, showed how lipids fit inside proteins using size-based mechanisms.

Combined, the structures and biochemistry detail rules about the size, shape, and chemical content of the kinds of lipids that can bind CD1 and cause a T cell response—either activation or deactivation. It is the latest in a series of studies that date back to the 1990s, when Brigham scientists discovered that T cells can recognise lipid antigens.

Splashdown“. The image provides a prism for thinking about how oily antigens are recognized in aqueous solution. Four lipid presenting molecules, CD1a, CD1b, CD1c and CD1d, including a three dimensional CD1-lipid complex, fall toward the surface of a blue and watery environment surrounding a T cell. Image credit: Dr Erica Tandori.

“In this ambitious decade-long, multidisciplinary study, we have characterized the full spectrum of cellular lipids that can be displayed to T cells. Further, we have collated 25 years of structural biology data, as well as new data collected at the ANSTO Australian Synchrotron, to standardize the rules that govern the molecular mechanisms in lipid presentation” said Dr Shahine. “Our hope is that the data generated in this study will serve as a foundation for future research in the field of lipid mediated immunity.”

Professor Moody said, “The Brigham provides an environment where physicians and scientists from differing fields can collaborate. This multidisciplinary effort involved biophysical techniques related to mass spectrometry and biological techniques related to lipid chemistry. The lipids informed immunological outputs, and the mode of lipid recognition is proven through X-ray crystallography.”

Read the full publication in Cell, titled CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms

DOI: 10.1016/j.cell.2023.08.022.

Original article

BDI researchers honoured in annual Dean’s Awards

Congratulations to Drs Adam Shahine and Milda Kaniusaite, who have each been recognised with a Dean’s Award for Excellence in 2021 for research carried out at the Monash Biomedicine Discovery Institute (BDI).

Dr Shahine won an award in the Excellence in Research – Early Career Researcher category.

“It was an honour to receive the ECR category for the Dean’s Excellence in Research award,” he said.

Dr Shahine has researched the immune system and its functions regulating and dysregulating immunity in our bodies since 2014 in Professor Jamie Rossjohn’s lab. “This work has provided a number of novel molecular insights into how presentation of lipid antigens plays a role in modulating adaptive immunity,” he said.

The research has been appeared in a number of high quality publications such as ‘Nature Cancer’ and ‘Science Immunology’, and been presented at conferences at places including the UK and US. “And that has all made an impact on the field,” Dr Shahine said. “Building upon this body of work, I was awarded an ARC DECRA Fellowship to continue research in this field to explore uncharted territory.”

Dr Shahine acknowledged the role of Professor Rossjohn in his career successes. “I definitely wouldn’t be where I am today without the mentorship of my supervisor Jamie Rossjohn, the supportive network within the laboratory, as well as collaborators at Harvard,” he said. The Australian Synchrotron has been invaluable, he added.

Dr Shahine is supervising three junior post-doc researchers and three PhD students, as well as conducting his own research.

Biochemist Dr Milda Kaniusaite’s research in the field of discovering new antibiotics earned her a Dean’s Award for Doctoral Thesis Excellence.

She said the exciting interdisciplinary project sought to understand the biosynthesis mechanism of clinically relevant antibiotics such as Teicoplanin and Vancomycin, then, based on these findings, re-engineer the biosynthesis pathway and demonstrate production of altered sequence products.

“This project was highly unique, given the fact that I was able to isolate whole antibiotic biosynthesis mega-enzymatic machinery from bacteria,” Dr Kaniusaite said. “In general, findings from my PhD can be considered as a set of rules that provide novel guidelines for effective biosynthetic pathway re-engineering leading to the synthesis of new molecules,” she said.

“The results from this study appear to be universal and can be relevant to the re-engineering of many other clinically important compounds produced by mega-enzymes. “This I believe will be of great importance in developing new drugs related to the treatment of antibiotic-resistant bacterias,” she said.

Dr Kanuisaite said it was a great pleasure and honour to win the award. “The award motivates and boosts my confidence that I am on the right track being a researcher and working for science. It helps me to open new doors, get new opportunities and gives an additional strength dealing with new and upcoming challenges.”

She is now a post-doctoral researcher at the Institute for Clinical Medicine at the University of Oslo, Norway.

The awards were given to 25 Monash Medicine, Nursing and Health Sciences individuals and team recipients for outstanding achievements in education, research, industry education programs, professional services, and doctoral thesis.

During the virtual event this month, Professor Christina Mitchell AO, Dean of Monash Medicine, Nursing and Health Sciences acknowledged the efforts of all staff and PhD graduates. “I would like to congratulate all of our award winners. You are an amazing group and outstanding in every way. I look forward to congratulating you in person soon,” she said.

Videos of this year’s winners discussing their projects and achievements can be viewed on the Dean’s Award for Excellence website.

About the Monash Biomedicine Discovery Institute at Monash University

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

Original article