About

M. Gregory Forest is the Grant Dahlstrom Distinguished Professor of Mathematics at the University of North Carolina at Chapel Hill. He holds joint appointments in Applied Physical Sciences and Biomedical Engineering and serves as the Director of the Carolina Center for Interdisciplinary Applied Mathematics. Additionally, he is the Associate Director of the Statistical & Applied Mathematical Sciences Institute. His dissertation was titled 'Multiple Phase Averaging of Periodic Soliton Equations,' and he was advised by David McLaughlin with Hermann Flaschka as co-advisor. His research focuses on applied mathematics, particularly in the areas related to interdisciplinary applied mathematics, soliton equations, and phase averaging.

Research topics

• Biology
• Computational biology
• Genetics
• Biophysics
• Cell biology

Selected publications

• Study of Protein-Protein Interactions in Septin Assembly: Multiple Amphipathic Helix Domains Cooperate in Binding to the Lipid Membrane

  Zenodo (CERN European Organization for Nuclear Research) · 2026-02-11

  datasetOpen access

  This repository contains data, analysis scripts, and figures used in the study of amphipathic helix (AH) domains in septin assembly. Using all-atom molecular dynamics simulations, the work explores how single and multiple AH peptides interact with lipid bilayers, including membrane-induced curvature, peptide bending, lipid packing defects, and peptide-peptide interactions. The findings contribute to understanding cooperative membrane binding and septin filament formation.

  PublisherDOI

• Charge distribution and helicity tune the binding of septin's amphipathic helix domain to membranes

  Biophysical Journal · 2025-04-01 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Design of High-Performance Viscoelastic Polymer Nanocomposites Using Stiff Nanorings

  Macromolecules · 2025-06-09 · 2 citations

  article

  The pursuit of polymer nanocomposites (PNCs) that simultaneously exhibit high strength and toughness has long been hindered by the intrinsic trade-offs between these properties. Here, we introduce a groundbreaking strategy by integrating stiff nanorings (SNRs) into polymer melts, enabling unprecedented mechanical performance without relying on traditional cross-linking or filler reinforcement. Through advanced statistical rheological simulations, we reveal that threading polymer chains through SNRs transforms the melt into a gel-like hyperviscous fluid, despite the absence of permanent or transient cross-links. Under applied strain, the dynamic sliding of polymer chains along the constrained SNRs concentrates stress on the nanorings, effectively delaying chain relaxation and minimizing chain breakage. This innovative mechanism not only enhances both strength and toughness but also imparts exceptional viscoelastic properties, surpassing those of conventional polymer melts. Our findings establish SNRs as dynamic stress-dissipative units, offering a versatile and scalable platform for designing next-generation PNCs. This work opens new avenues for applications in extreme mechanical environments, from advanced manufacturing to biomedical engineering, and represents a paradigm shift in PNC science.

  PublisherDOI

• Tuning nuclear rheology through transient chromatin cross-links

  Physical review. E · 2025-11-17 · 1 citations

  articleOpen access

  In eukaryotic cells, the nucleolus is a pivotal subnuclear organelle, instrumental in ribosomal RNA synthesis and nuclear organization. Although the unique viscoelastic properties of the nucleolus are associated with transient interactions between chromatin and regulatory proteins, the specific mechanistic details driving nucleolar phase separation and mechanical responses have remained largely undefined. In this study, we employ a computational approach to elucidate chromatin-protein interactions within the nucleolus of budding yeast, using a sophisticated bead-spring polymer model. This model integrates DNA and nucleolar architectures with dynamic simulations of interactions involving chromosomal structural maintenance proteins and rDNA transcriptional regulators through systematically varied cross-linking kinetics. Our findings reveal that modulations in protein-DNA interactions critically dictate the phase behavior, relaxation dynamics, and viscoelastic properties of the nucleolus, underscoring a complex but precise regulatory mechanism at play. Notably, protein-mediated bridging emerges as a critical factor enhancing nucleolar condensation and modulating stress relaxation, highlighting the transformative role of transient cross-linking in nuclear mechanics regulation. These insights not only deepen our understanding of nucleolar function but also open avenues for interventions in genetic engineering and disease therapeutics.

  PublisherOA PDFDOI

• Modeling insights into SARS-CoV-2 respiratory tract infections prior to immune protection

  UNC Libraries · 2025-05-06

  articleOpen access
  PublisherDOI

• The Role of Transient Crosslinks in the Chromatin Search Response to DNA Damage

  UNC Libraries · 2025-12-12

  articleOpen access

  Homology search is a means through which DNA double-strand breaks (DSBs) explore the genome for sequences that enable error-free repair, known as homologous recombination. A better understanding of this search process is fundamental to the relationship between higher-order chromosome organization and DNA damage. Here, we use an entropic bead-spring polymer chain model to simulate the spatiotemporal dynamics of the yeast genome during interphase. The chromosome is organized by transient and dynamic cross-links representing structural maintenance of chromosome (SMC) complexes. DNA damage is modeled as a break in the bead-spring chain, coupled with a removal of crosslinks from beads proximal to the break site. We show that the removal of cross-links drives the exploration of genomic space by the damaged ends, while rates and densities of intact dynamic crosslinking have only a minor role. Local depletion of SMC cross-links proximal to the break site enables the damaged segment to escape the chromosome territory and enhances its ability to explore the genome. Our study reveals a foundational principle by which DSBs can encounter distant regions of sequence homology.

  PublisherDOI

• Modeling identifies variability in SARS-CoV-2 uptake and eclipse phase by infected cells as principal drivers of extreme variability in nasal viral load in the 48 h post infection

  UNC Libraries · 2025-02-22

  articleOpen access
  PublisherDOI

• Study of Protein-Protein Interactions in Septin Assembly: Multiple amphipathic helix domains cooperate in binding to the lipid membrane

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-12

  preprintOpen access

  Septins are a conserved family of cytoskeletal proteins known for sensing micron-scale membrane curvature via amphipathic helix (AH) domains. While cooperative interactions in septin assembly have been suggested, the molecular mechanisms governing membrane binding and assembly remain unclear. Building on prior findings, we use all-atom molecular dynamics simulations to examine how single and paired extended AH domains, derived from Cdc12, interact with lipid bilayers. We find that a single membrane-bound AH adopts a bent conformation upon membrane association. In solution, a second AH peptide preferentially interacts with the bound peptide through conserved salt bridges, favoring an antiparallel arrangement. Simulations of covalently linked AH tandems confirm the stability of this configuration. When two AH domains are membrane-bound, they induce localized lipid packing defects, reduce tail order, and exhibit slight peptide displacement on planar bilayers. These observations suggest a cooperative AH binding mechanism and are consistent with models in which lipid packing defects facilitate multivalent AH engagement in curved membrane environments. Our findings advance the mechanistic understanding of septin-membrane interactions and highlight the role of cooperative AH domain binding in stabilizing higher-order structures.

  PublisherDOI

• BPS2025 - The role of AH domains in cooperative septin assembly: Molecular dynamics reveals a role for protein-protein interactions in membrane binding

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• The Role of Transient Crosslinks in the Chromatin Search Response to DNA Damage

  International Journal of Molecular Sciences · 2025-12-03

  articleOpen accessCorresponding

  Homology search is a means through which DNA double-strand breaks (DSBs) explore the genome for sequences that enable error-free repair, known as homologous recombination. A better understanding of this search process is fundamental to the relationship between higher-order chromosome organization and DNA damage. Here, we use an entropic bead-spring polymer chain model to simulate the spatiotemporal dynamics of the yeast genome during interphase. The chromosome is organized by transient and dynamic cross-links representing structural maintenance of chromosome (SMC) complexes. DNA damage is modeled as a break in the bead-spring chain, coupled with a removal of crosslinks from beads proximal to the break site. We show that the removal of cross-links drives the exploration of genomic space by the damaged ends, while rates and densities of intact dynamic crosslinking have only a minor role. Local depletion of SMC cross-links proximal to the break site enables the damaged segment to escape the chromosome territory and enhances its ability to explore the genome. Our study reveals a foundational principle by which DSBs can encounter distant regions of sequence homology.

  PublisherOA PDFDOI

Recent grants

• Collaborative Research: Collaborative Proposal for Mathematics & Computation of Nano-Composite Flows & Properties

  NSF · $213k · 2006–2009

• Collaborative Research: A Molecular-to-Continuum, Data-Driven Strategy for Mucus Transport Modeling

  NSF · $100k · 2014–2017

• A Mathematical-Experimental Strategy to Discern the Molecular Basis of "Successful Mucus"

  NSF · $960k · 2015–2019

• RAPID: A Lung Mucus Strategy for COVID-19 Viral Protection

  NSF · $200k · 2020–2021

• Big Data to Knowledge Training Program

  NIH · $851k · 2015–2020

Frequent coauthors

• Samuel K. Lai

  University of North Carolina at Chapel Hill

  89 shared

• David B. Hill

  North Carolina State University

  83 shared

• Ruhai Zhou

  Xiangya Hospital Central South University

  50 shared

• Ronit Freeman

  Applied Physical Sciences (United States)

  45 shared

• Timothy Wessler

  43 shared

• Paula A. Vasquez

  University of South Carolina

  38 shared

• Jay Newby

  University of Alberta

  36 shared

• Matthew R. Markovetz

  University of North Carolina at Chapel Hill

  36 shared