# Deciphering fundamental biological processes involving protein-nucleic acid interactions at the molecular level

> **NIH NIH R35** · DUKE UNIVERSITY · 2020 · $581,930

## Abstract

ABSTRACT
The central focus of the Schumacher laboratory is to deduce molecular principles that govern fundamental
biological processes involving protein-nucleic acid interactions. Our recent work has honed in on transcription
networks and DNA segregation in microbes. The latter studies have uncovered key insights into the molecular
mechanisms utilized by simplified systems employing actin-like and tubulin-like NTPases to segregate bacterial
plasmids. However, the molecular mechanism(s) controlling the most common bacterial segregation systems,
the Walker-box based systems, remain unclear and represent a major focus of our research. Strikingly, our
recent studies characterizing the first archaeal segregation system revealed that it utilizes a bacterial-like
Walker-box NTPase to drive DNA segregation, indicating that Walker-box segregation machineries may be the
most ubiquitous type of DNA segregation modules in biology. These investigations also revealed that the
archaeal segregation ParB protein harbors a fold similar to CenpA, the histone homolog that mediates DNA
segregation in eukaryotes. Thus, these studies uncovered possible evolutionary linkages in segregation
machineries between the 3 domains of life. Our most recent work has provided the first molecular views of
Walker-box NTPases bound to DNA and ParB. These data combined with cellular and biochemical studies
have allowed us to propose a general, non-polymer based model for Walker-box segregation that we will test
using cellular and molecular approaches. Our work on the nitrogen regulatory circuitry in B. subtilis has
revealed new DNA binding modalities and a novel regulatory mechanism involving the direct enzyme of
nitrogen homeostasis, glutamine synthetase. A new direction for the lab is to deduce the molecular
mechanisms controlling Streptomyces development, which coincides with their production of antibiotics
(secondary metabolites). Indeed, Streptomyces generate most of our current antibiotics as well as a plethora of
biomedically important compounds. In the next 5 years we will expand on these efforts, but also add cellular,
genetic and cryo-EM microscopy approaches to provide a more complete picture of these systems. These
investigations notably intersect with the lab's interests in microbial multidrug resistance and multidrug
tolerance. Indeed, while the overall goals of these studies are to determine fundamental biological principles
these ongoing studies will also provide novel targets for the development of antimicrobial therapeutics, which
are urgently needed given the alarming rise of multidrug resistant microbes and the scarcity of new
antimicrobials in the pipeline.

## Key facts

- **NIH application ID:** 9843152
- **Project number:** 5R35GM130290-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Maria Schumacher
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $581,930
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843152

## Citation

> US National Institutes of Health, RePORTER application 9843152, Deciphering fundamental biological processes involving protein-nucleic acid interactions at the molecular level (5R35GM130290-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843152. Licensed CC0.

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