# Non-genetic inheritance: mechanisms of microbiome-mediated transgenerational change

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $15,372

## Abstract

Project Summary
The dense microbial communities associated with animals, referred to as the microbiome, can have
an important impact on both host development and physiology. Yet, we are only beginning to
understand the mechanisms by which the microbiome promotes these important functions. There is
great interest to define and understand how these associations, such as changes in composition, or
dysbiosis, are linked to a number of diseases. Moreover, the ability to manipulate or restore the
microbiome is being pursued as a therapeutic target. While the success of fecal transplant therapy for
acute and chronic Clostridium difficile infections highlights their potential, the broader applicability of
such therapies to other maladies remains unknown. Consequently, there is great need to understand
the relationship between a host and its microbiome with regards to its regulation and molecular
signaling mechanisms. I propose to utilize the fruit fly, Drosophila melanogaster, to investigate
mechanisms that contribute to the establishment of normal host physiological conditions, a critical
step in developing strategies for microbiome therapy. My project will focus on the timing and
establishment of normal parameters of host physiology and development. Specifically, I will study in
germ-free flies and flies that have experienced early-life events that disrupt the microbiome, the latter
of which has been linked to chronic diseases in other animal models. The specific goals of this
proposal are to: a) Explore the trans-generational impacts of the microbiota on D.
melanogaster. b) Identify host and microbiota factors that promote normal host physiology. c)
Develop strategies to restore normal animal physiology through manipulation of the
microbiome. I will use high throughput sequencing technologies in the form of transcriptomes,
metabolomes, and epigenomes to investigate gene expression and metabolite production across fly
development and through generations, coupled with traditional genetic approaches to characterize
identified targets. My experiments will focus on comparisons with germ-free, gnotobiotic, and
conventionally-reared flies to characterize the effects of host association with the microbiome. I will
also identify microbial signals that induce changes in the host and will experimentally manipulate both
the host and microbial recognition and signaling systems that mediate these associations. Given the
high conservation of developmental and homeostatic signaling pathways between files and humans,
and that 75% of known human disease genes have a match in the D. melanogaster genome, I
anticipate that this work will identify conserved mechanisms that regulate host-microbiome
interactions in all animals, including humans.

## Key facts

- **NIH application ID:** 9964859
- **Project number:** 5R35GM128871-03
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** NICHOLE A BRODERICK
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $15,372
- **Award type:** 5
- **Project period:** 2018-07-20 → 2020-08-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964859

## Citation

> US National Institutes of Health, RePORTER application 9964859, Non-genetic inheritance: mechanisms of microbiome-mediated transgenerational change (5R35GM128871-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964859. Licensed CC0.

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