# Self-nonself recognition and multicellularity in myxobacteria

> **NIH NIH R35** · UNIVERSITY OF WYOMING · 2021 · $287,194

## Abstract

Abstract
 A fundamental question in biology is how individual cells within a multicellular organism
recognize other cells as self to cooperatively function in tissues, organs and as whole individuals.
To address this complex question, we study a relatively simple and experimentally trackable
model organism, Myxococcus xanthus. Although a bacterium, M. xanthus exhibits many traits
found in tissues and more complex multicellular species. One trait is multicellular development in
response to starvation. Another trait, we discovered, is the ability of cells to distinguish between
self and nonself for the exchange of cellular proteins and lipids. Recognition is mediated by a
polymorphic cell surface receptor called TraA and its partner TraB. Only cells that bear identical
or nearly identical TraA receptors engage by homotypic interactions. Social outcomes from this
process, called outer membrane exchange (OME), vary depending on the properties of the
interacting cells. In some cases, OME leads to cooperative interactions whereby healthy donors
repair damaged cells by replenishing their cell components. In other cases, OME leads to
antagonism when partnering cells are not clonal. Discrimination occurs by polymorphic toxin
transfer to recipient cells that lack cognate immunity.
 Our future goals are multifaceted with respect to understanding OME and, more broadly, how
cells recognize self and transition toward multicellularity. Over the next five years we will critically
examine how OME leads to cooperativity. One area of investigation is how TraA/B directs
emergent behaviors in populations that include synchronized and coordinated movements. This
will be explored by monitoring global gene expression and how TraA/B interacts with a signal
transduction pathway that controls motility. Cell synchronization is being studied with a biosensor
the monitors’ calcium fluxes in cells. Other approaches will probe how M. xanthus responds and
adapts to environmental stresses, whereby those adaptations are transferred to naïve populations
by OME. A second area of research addresses how myxobacteria rapidly diverge into different
social groups in natural environments. Our preliminary findings indicate that horizontal gene
transfer by non-lytic transducing particles mediate population divergence by carrying polymorphic
genes involved in social discrimination. A third focus area will elucidate the mechanism of OME
thought to involve outer membrane fusion. Finally, we will explore new mechanisms of self-
recognition and its role in multicellular life.

## Key facts

- **NIH application ID:** 10167491
- **Project number:** 1R35GM140886-01
- **Recipient organization:** UNIVERSITY OF WYOMING
- **Principal Investigator:** DANIEL WALL
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $287,194
- **Award type:** 1
- **Project period:** 2021-05-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167491

## Citation

> US National Institutes of Health, RePORTER application 10167491, Self-nonself recognition and multicellularity in myxobacteria (1R35GM140886-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10167491. Licensed CC0.

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