isbscience.org/research/wilke-lyme-disease-project/Lyme Disease: A 21st Century Approach
“ISB is taking the first ‘systems approach,’ or holistic view, of Lyme disease – examining the genomics and proteomics of the organism, the host immune response to the infection, and identifying critical biomarkers from the blood – to assess and direct future treatment of this devastating disease.
We are also proposing to do dense phenotyping of Lyme disease patients to discover and solve heretofore hidden mysteries of the infection as it is initiated, as it progresses, and as it responds – or fails to respond – to treatment.”
-Dr. Leroy Hood, ISB co-founder
WHY NOW?
- Officials believe that the actual incidence of cases of Lyme disease is about 300,000, a number that is 10 times more than the CDC has reported.
- The number of cases reported annually increased nearly 25-fold since 1982 when national surveillance began.
- The causes of debilitating chronic Lyme disease are not yet understood.
WHAT WE KNOW
Our researchers have put their efforts into looking at Lyme disease and the bacteria, Borrelia burgdorferi, that causes the disease, through the lens of systems biology, and utilizing approaches pioneered at ISB to gather, synthesize and interpret large and complex datasets.
To date, our researchers have:
- Undertaken a longitudinal study in which people with newly diagnosed Lyme disease provided blood and urine specimens at several set time points that allow us to track resolution of the disease or progression to post-treatment symptoms. Deep multi-omic analyses of these samples will reveal clinically useful biomarkers, immunological correlates, vaccine targets, and possibly new therapeutic targets.
- Discovered potential human biomarkers at the protein and RNA level.
- Analyzed evolution of the immune response during Lyme disease.
- Optimized methods for growing large quantities of the infective clinical strains of Borrelia bacteria in the lab, which will provide materials for deep multi-omic analyses of the pathogen.
- Performed an in-depth proteomic and genomic analysis of Borrelia bacteria to define coat proteins with the ultimate goals of developing methods for direct detection of the Borrelia pathogen in patients (i.e., for early stage diagnosis) and identifying novel potent vaccine targets.
- Developed a robust informatics pipeline for analyzing the genome sequence of Borrelia, performed deep genome analysis of six Borrelia strains, and are poised to analyze many more.
- Collaborated with several organizations, including New York Medical College, Bay Area Lyme Foundation, Mass General Hospital, Johns Hopkins University and Mount Sinai.
MAKING OUR MARK
PROTEIN AND RNA BIOMARKER PANELS
Enable us to diagnose Lyme disease earlier, to identify patients most likely to progress to long-term symptoms, and to provide information about which organs are most affected by Borrelia infection.
Patent filed on these discoveries, manuscripts in preparation for peer-reviewed publication.
BORRELIA GENOME ANALYSIS
Defining the blueprint of all genes and their variants present in different infective strains of the bacteria.
Two manuscripts accepted for publication, additional manuscripts submitted or in preparation.
LONGITUDINAL ANALYSIS
Longitudinal analysis of Lyme disease patients has revealed novel signatures of the immune response to infection.
Multiple manuscripts in preparation.
BORRELIA PROTEOMICS
In-depth quantitative profiling of all proteins expressed in Borrelia to understand what makes one strain more infectious than another.
Borrelia PeptideAtlas and SRMAtlas: Comprehensive catalogs of all proteins expressed and defined quantitative assays, a valuable open resource for the research community.
PUBLICATIONS
- Jabbari, N., Glusman, G., Joesch-Cohen, L.M., Reddy, P.J., Moritz, R.L., Hood, L., Lausted, C.G., 2018. Whole genome sequence and comparative analysis of Borrelia burgdorferi MM1. PLOS ONE 13, e0198135. https://doi.org/10.1371/journal.pone.0198135
- Malge, A., Ghai, V., Reddy, P.J., Baxter, D., Kim, T.-K., Moritz, R.L., Wang, K., 2018. mRNA transcript distribution bias between Borrelia burgdorferi bacteria and their outer membrane vesicles. FEMS Microbiol. Lett. 365. https://doi.org/10.1093/femsle/fny135
HOW YOU CAN HELP
We have made great strides in understanding Lyme disease and creating an infrastructure to disseminate our findings in a relevant and timely manner. But our work is far from done. Your support is critically important to our quest to end Lyme disease. To learn more about the disease, or to fuel our research, please visit isbscience.org/donate-to-lyme-research, or contact:
Renee Duprel | 206.732.1287 | renee.duprel@isbscience.org
