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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

Read about our disability internship program featured by WISE Employment

Rossjohn Laboratory pioneers inclusive paid internship program for GradWISE graduates

In a display of commitment to diversity and inclusion, Rossjohn Laboratory, a renowned Biomedical Science research lab in Australia, has taken significant strides to create a more inclusive workplace and support newly emerging graduates with disabilities. As a longstanding partner of GradWISE, the organisation has recently offered multiple disability-affirmative paid internship positions to graduates from various universities, marking a ground-breaking moment for the scientific community.

Four GradWISE science graduates secured the highly sought-after internship opportunities at Rossjohn Laboratory. Over the past 12 weeks, they have been welcomed into the research and administrative teams, immersing themselves in the inner technical workings of the cutting-edge laboratory.

GradWISE graduates interning at Rossjohn Laboratory

Leading this initiative is Professor Jamie Rossjohn, FAA FAHMS FLSW FMedSci FRS, an ardent advocate for workplace diversity. Professor Rossjohn’s unwavering commitment to creating broader internship opportunities for graduates with disabilities has set a shining example for the scientific community. He firmly believes that by fostering diversity in the workplace, not only does the team benefit from a wider range of perspectives and ideas, but it also leads to enriched experiences for all involved.

“Collaborating with the Rossjohn Lab has been an incredibly enriching experience for GradWISE participants. Their dedication to fostering inclusion and providing meaningful opportunities is truly commendable. Together, we’ve opened doors for talented individuals to contribute to groundbreaking projects” says Head of GradWISE Edward Osano.

During their internship, they have had the privilege of participating in the Monash Sensory Science Exhibition held in June. The exhibition, which brings together art and science for participants with diverse needs, provided an inspiring platform for the interns to showcase their skills and passion for scientific discovery.

The experience at Rossjohn Laboratory has proven to be transformative for the interns, giving them greater confidence in navigating the workplace and reinforcing their passion for scientific research. One intern, who had never been employed before, expressed immense excitement and eagerness to continue contributing to the lab as part of their ongoing career journey.

GradWISE student Sophia says “working for Rossjohn Laboratory has long been a goal of mine. I was so excited to secure the internship with assistance from GradWISE. Assisting the team to deliver the Monash Sensory Science Exhibition has helped improve my confidence and broaden my skills. I felt supported every step of the way. I’m so grateful to Professor Rossjohn and the team for this opportunity.”

Professor Rossjohn, while discussing the remarkable progress of the GradWISE interns, was filled with pride and admiration for their contributions. In recognition of their exceptional performance, he provided the GradWISE interns with an additional six-week contract extension, underscoring the laboratory’s commitment to nurturing talent and providing meaningful opportunities.

science objects at Rossjohn LaboratoryOver the last three months, Coach Roanna Harry has been there to provide support to the GradWISE participants.

“The Monash Sensory Science Exhibition was an impressive display of inclusive creativity and innovation. It was wonderful to see the Rossjohn interns in action as they assisted the team to run the event. It’s been so heart-warming to see our students thrive and witness their professional growth over the course of the internship. The nurturing and inclusive culture within the Rossjohn team has been crucial to their success. As they near the end of the internship, GradWISE look forward to continuing to support our participants to leverage this once-in-a-lifetime opportunity, as they embark on careers in the science field” says Roanna.

[Images:  1. Sean Christopher (L) and Sophia Ladanyi (R) assisting at the Monash Sensory Science exhibition on June 30th, 2023.  2. Tactile models of immunity created for the exhibition.]

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