2018 Michelson Prizes Research Highlights: Illing, Satpathy, Mackay.
The 2018 Michelson Prizes Research Highlights place the spotlight on the findings of 3 three young scientists: Dr. Patricia Therese Illing (Monash University), Dr. Ansuman Satpathy (Stanford University), Dr. Laura Kate Mackay (Peter Doherty Institute for Infection and Immunity). Previously, in 2017, the Michelson Medical Research Foundation joined the Human Vaccines Project to fund an exciting new initiative—the Michelson Prizes for Human Immunology and Vaccine Research. With the advent of the Michelson Prizes, the Michelson Medical Research Foundation founder Dr. Gary Michelson hoped to give support to new investigators while facilitating vaccine discovery.
Challenges Faced by New Investigators
New investigators are often challenged to obtain initial research funding as they must compete with more established and experienced investigators in their fields. Funding institutions also shy away from innovative, outside-the-box thinking if it lacks a surfeit amount of preliminary data. The Michelson Prizes give young investigators a chance to explore more high-risk, high-reward avenues of research in the area of human immunology and vaccine research. 
The first Michelson Prizes were awarded in June 2018 as part of a scientific conference on the Convergence of Human Immunology and Vaccine Research hosted at the USC Michelson Center for Convergent Bioscience at the University of Southern California. As part of the conference, each award winner presented their unique, innovative approach for advancing vaccine research. 
2018 Michelson Prizes Research Highlights #1
Dr. Patricia Therese Illing: Dissecting the Role of Splice Peptides in Influenza Vaccination
Dr. Patricia Therese Illing is a research fellow of biochemistry and molecular biology at Monash University in Melbourne, Australia. Dr. Illing’s research focuses on how cells in the body show the immune system that they have become infected with a virus or pathogen. She is interested in how a novel class of peptides contributes to the immune response for influenza, an underestimated but deadly virus.
All cells have a variety of peptides present on their surface. Proteins in the cell are processed by the proteasome to produce small peptides which then become associated with the human leukocyte antigen class I (HLAI) protein and are sent to the cell surface as a protein complex. This presents a summary of the cell’s protein production, or immunopeptidome, to the surrounding cellular environment.
If a virus infects a cell, it will stimulate viral protein production and viral proteins will become present on the infected cell’s surface. This should be recognized by the immune system, stimulate a T cell response, and help to eliminate the infected cell.
The immunopeptidome can be sequenced and analyzed. However, in the last decade, researchers realized that they were neglecting an entire class of peptides that could not be identified using standard mass spectrometry protein sequencing methods.
(Fig.1) Slide from Spliced Peptides — Novel Candidates for Effective Influenza Immunity? as presented by Dr. Patricia Therese Illing during the 1st Annual Conference on the Future of Vaccine Development located at the USC Michelson Center for Convergent Bioscience on June 27th, 2018.
This novel class of peptides called spliced peptides are created in the proteasome by a process called transpeptidation which stitches different peptides together (Figure 1). This creates a much more diverse array of proteins that are presented on the surface of the cell with HLAI. New mass spectrometry techniques have revealed that approximately 30% of immunopeptidome peptides were created by peptide splicing.
Dr. Illing and her research group developed a more efficient method for identifying spliced peptides and identified viral peptide splicing products in cell lines infected with the influenza virus. They are now working to define the rules for peptide splicing and cell surface peptide presentation for the influenza virus. Their future research goals involve developing better vaccines that allow the body to more efficiently identify influenza-infected cells. 
2018 Michelson Prizes Research Highlights #2
Dr. Ansuman Satpathy: Harnessing the Power of Genomics, Computer Science, and Engineering to Improve Patient Care
Dr. Ansuman Satpathy is an Assistant Professor of Pathology at Stanford University in Stanford, California. His research aims to discover how non-protein-coding DNA affects the expression levels of disease-related genes in patients. Dr. Satpathy hopes to combine research from the fields of genomics, computer science, and engineering to create solutions that directly improve patient care.
Although non-coding DNA was once considered “junk” DNA, researchers are now appreciating its important role in human biology. Genome-wide association studies have shown that the majority of disease risk arises from non-coding regions in the genome. This is achieved when non-coding DNA regions interact with coding regions and affect gene expression levels. Non-coding regions that increased gene expression are called enhancers and typically interact with gene promoters.
(Fig.2) Slide from 3D and Single-Cell Epigenome Technologies for Precision Immune Profiling as presented by Dr. Ansuman Satpathy during the 1st Annual Conference on the Future of Vaccine Development located at the USC Michelson Center for Convergent Bioscience on June 27th, 2018.
Dr. Satpathy and his research group are working to identify disease-associated enhancer-promoter interactions on a genome-wide scale. However, this is not a simple task—interacting sequences can sometimes be megabases apart. Dr. Satpathy has developed and refined new technologies that allow for rapid sequencing and mapping of enhancer-promoter interactions. The assays are more powerful than previous technologies—interactions can be identified at high resolution with only 50,000 cells compared to the millions of cells required for previous techniques (Figure 2).
Dr. Satpathy is currently working to engineer enhancers to treat autoimmune diseases using genome editing techniques like CRISPR to strengthen enhancer-promoter interactions. Ultimately, Dr. Satpathy and his research group would like to use this approach to identify why vaccines work well in some patients and not others. 
2018 Michelson Prizes Research Highlights #3
Dr. Laura Kate Mackay: Using Trm Cells to Improve Vaccination Strategies
Dr. Laura Kate Mackay is a Laboratory Head and Senior Lecturer of Microbiology and Immunology at the Doherty Institute in Melbourne, Australia. She is interested in a special subset of immune cells called tissue-resident memory T (Trm) cells. When T cells first detect an antigen, a large pool of activated T cells is generated. The large pool will then contract to leave memory T cells that continue to protect against infection. This is the principle that underlies vaccination.
Researchers have primarily focused on the population of T cells that circulate throughout the body. However, in the past decade, Trm cells have emerged as a key player in the immune response. Trm cells are critical for local immunity in protecting against infections and cancer. Dr. Mackay and her research group demonstrated that mice embedded with Trm cells in the skin were able to resist herpes simplex virus infection more successfully than mice who were given a boost of circulating T cells. An increase in the number of Trm cells embedded in the skin led to greater viral resistance. Work with collaborators also found that Trm cells are associated with better prognosis against cancer.
(Fig.3) Slide from Targeting Tissue-Resident Immune Cells for Enhanced Immune Protection as presented by Dr. Laura Kate Mackay during the 1st Annual Conference on the Future of Vaccine Development located at the USC Michelson Center for Convergent Bioscience on June 27th, 2018.
To better understand Trm cells, Dr. Mackay is working to uncover the factors that regulate Trm cell development. Trm differentiation is a complex, multistep process (Figure 3), but Dr. Mackay has identified a host of genes that are required for Trm cell development and she has shown that Trm specific genes can be targeted to increase Trm cell deposits.
Dr. Mackay hopes to take advantage of Trm cells to create more robust vaccination strategies. Trm cells clearly offer protective power against viral infections and cancers. Her future research will focus on harnessing this power to develop the next generation of vaccinations and cancer immunotherapies. 
Upcoming 2019 Michelson Prizes
The Michelson Prizes are continuing in 2019. Submitted applications are currently under review. The 2019 Michelson Prizes will focus on the research areas of Human Immunology, Computational Biology and Protein Engineering, and Neglected Parasitic Diseases in the context of furthering vaccine and immunotherapy discovery.
- Michelson Prizes: Human Immunology & Vaccine Research [HVP] | MMRF
- Michelson Vaccine Development Conference [HVP/USC] | MMRF
- 2018 Vaccine Development Conference Session #05: Spliced Peptides [2018-06-27. Patricia Therese Illing, Marie-Paule Kieny. HVP/USC]
- 2018 Vaccine Development Conference Session #10: Precision Immune Profiling [2018-06-27. Ansuman Satpathy, Peggy Hamburg. HVP/USC]
- 2018 Vaccine Development Conference Session #14: Immune Protection Enhancement [2018-06-27. Laura Kate Mackay, Stanley Plotkin. HVP/USC]