# Microbial Determinants of Clinical Heterogeneity in Lyme Disease

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $136,350

## Abstract

Lyme disease is an emerging public challenge due to its increasing incidence, expanding geographic range,
and heterogeneous clinical manifestations that may involve the skin, nervous system, heart, and joints. The
disease is caused by spirochetes of the genus Borreliella (previously referred to as the Borrelia burgdorferi
sensu lato group), a diverse group that contains over 20 species, four of which commonly affect humans.
Clinical disease varies on the basis of the infecting species, yet the specific microbial factors that mediate
these effects are not known. To identify such genes, the candidate and co-mentors have begun conducting
genomic association studies of Borreliella spp. from patients. These preliminary studies have revealed a
number of promising candidate loci that are associated with distinct clinical manifestations of Lyme disease.
This proposal is a career development award that provides a pathway to independence and includes a
24-month mentored phase followed by a 24-month independent phase. In Aim 1, the candidate will conduct
whole genome sequencing using hybrid assembly of short- and long-read sequences to produce finished
assemblies for hundreds of Borreliella spp. genomes from patients and perform evolutionary and population
genetic analyses to identify variants that may influence clinical manifestations. In Aim 2, the candidate will
conduct genetic association studies of Lyme disease spirochetes to identify microbial lipoproteins associated
with distinct clinical manifestations. As a part of this Aim, the candidate will develop imputation methods for
publicly available genomic data and also develop target capture methods that enable whole-genome
sequencing without microbial culture. In Aim 3, the candidate will characterize the mechanisms of
pathogenesis of a prioritized subset of the newly-identified loci using laboratory models.
The candidate is a physician-scientist and current Clinical and Research Fellow in Infectious Disease at
Massachusetts General Hospital (MGH) with an interest and background in tick-borne disease pathogenesis
and genomics. The proposed training and research plan will take place under the guidance of primary mentor
Dr. Pardis Sabeti and secondary mentors Dr. John Leong, Dr. Allen Steere, and Dr. Klemen Strle. The mentor
team brings together leading investigators with complementary expertise in microbial genomics (Dr. Sabeti),
bacterial pathogenesis (Dr. Leong), and clinical studies of Lyme disease (Dr. Strle and Dr. Steere). The work
will be carried out in a supportive, collaborative environment at MGH, the Broad Institute, and Tufts University
that will foster training and research. Completion of the proposed plan will position the candidate to lead an
independent, NIH-funded research program that performs basic, translational, and clinical studies of Lyme
disease and other tick-borne pathogens.

## Key facts

- **NIH application ID:** 10223164
- **Project number:** 5K99AI148604-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jacob Eric Lemieux
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $136,350
- **Award type:** 5
- **Project period:** 2020-07-24 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223164

## Citation

> US National Institutes of Health, RePORTER application 10223164, Microbial Determinants of Clinical Heterogeneity in Lyme Disease (5K99AI148604-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10223164. Licensed CC0.

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