Biology subjects

McGuinness, B.

Publications and source records attributed to McGuinness, B..

4 recordsLinked to original sources

bioRxiv2026

A winding road to coexistence: Interdependence of niche and fitness differences in E. coli with targeted resource uptake gene deletions

Resource competition theory typically assumes static traits and continuous supply of resources. Yet microbial communities often experience feast-famine cycles and rapid trait change. To investigate coexistence under these nonequilibrium conditions, we integrate modern coexistence theory (MCT) with a genome-scale metabolic model that explicitly links resource use (traits) to metabolic fluxes and growth. MCT partitions competitive interactions into niche and fitness differences, to predict when trait-driven departures from neutrality result in coexistence or exclusion. Using dynamic flux balance analysis, we define a function that maps trait-resource matching to niche and fitness differences between species in a two-species two-resource system. This mapping shows that niche and fitness differences are not independently tunable under resource competition: changes in transporter-mediated resource uptake and changes in resource concentration ratios generate constrained trajectories through coexistence space. Specifically, we show that the minimum niche difference required for coexistence increases linearly with the absolute difference in maximal growth rates on limiting resources, showing how limiting similarity between species can emerge from intracellular metabolic constraints. Furthermore, we find that in batch culture simulations, initial conditions (inoculum size, total resource concentration) determine the timescale of the transient growth phase, with niche differences saturating and fitness differences increasing as the timescale grows, thereby governing competition outcomes. Finally, we test these predictions experimentally using E. coli strains with targeted resource transporter knockouts under both equal and skewed resource concentrations. Our results confirm that transporter-mediated trait changes and resource concentration ratio modulation can be harnessed to engineer coexistence. Together, our work demonstrates that trait-resource matching imposes structured constraints on the joint evolution of niche and fitness differences, thereby shaping biodiversity maintenance in microbial communities under nonequilibrium conditions.

ecology↗

bioRxiv2025

Investigation of anti-SARS CoV-2 multimeric bicyclic peptide inhibitors in a range of pre-clinical therapeutic settings

The spread of respiratory viruses, such as Influenza and SARS-CoV-2 has presented significant challenges over the last 30 years with few effective therapeutic options available to this day. Bi-cyclic peptides represent a unique, modular, modality in the antiviral armamentarium against future pandemics. This study provides a deeper evaluation of multivalent bi-cyclic (Bicycle(R)) molecule efficacy in several preclinical SARS-CoV-2 challenge settings. We explore both pre-exposure prophylaxis and post-exposure therapeutic settings via subcutaneous and intranasal routes of administration. We contextualize this further in bespoke scenarios of immune compromisation, and viral transmission. Promisingly, in all studies we observe efficacy, significantly reducing infectious viral burden at each study endpoint. These data further support candidacy of Bicycle molecules as a differentiated antiviral therapeutic class in the context of pandemic preparedness. ImportanceThe COVID-19 pandemic, triggered a rapid wave of innovation, accelerating the delivery of new vaccine technology and anti-viral treatments. In our first paper, we described the discovery and molecular optimization of Bicycle molecules as a novel drug class for the potential treatment of SARS CoV-2. Here, we have performed deeper characterization of these molecules in established animal models that simulate SARS-CoV-2 transmission, testing more convenient delivery routes, such as intra-nasal. The Bicycle molecules demonstrated positive outcomes in each of these studies and suggest that Bicycle molecules, as convenient and effective anti-viral treatments, could be an important addition to help future preparedness against new viral pandemics.

pharmacology and toxicology↗

bioRxiv2024

Resource-use plasticity governs the causal relationship between traits and community structure in model microbial communities

Resolving the relationship between species traits and their relative abundance is a central challenge in ecology. Current hypotheses assume relative abundances either result from or are independent of traits. However, despite some success, these hypotheses do not integrate the reciprocal and feedback interactions between traits and abundances to predictions of community structure such as relative abundance distributions. Here we study how plasticity in resource-use traits govern the causal relationship between traits and relative abundances. We adopt a consumer-resource model that incorporates resource-use plasticity that operates to optimize organism growth, underpinned by investment constraints in physiological machinery for acquisition of resources. We demonstrate that the rate of plasticity controls the coupling strength between trait and abundance dynamics, predicting species relative abundance variation. We first show how plasticity in a single species in a community allows all other non-plastic species to coexist, a case of facilitation emerging from competitive interactions where a plastic species minimizes its similarity with competitors and maximizes resource-use efficiency in its environment. We apply this environment-competition trade-off to predict trait-abundance relationships and reveal that initial traits are better predictors of equilibrium abundances than final trait values. This result highlights the importance of transient dynamics that drive species sorting. The temporal scale of transients determines the strength of species sorting due to the emergence of ecological equivalence at equilibrium. We propose trait-abundance feedback as an eco-evolutionary mechanism linking community structure and assembly, highlighting trait plasticitys role in community dynamics.

ecology↗

bioRxiv2019

Single-molecule visualization of the effects of ionic strength and crowding on structure-mediated interactions in supercoiled DNA molecules

DNA unwinding is an important cellular process involved in DNA replication, transcription and repair. In cells, molecular crowding caused by the presence of organelles, proteins, and other molecules affects numerous internal cellular structures. Here, we visualize plasmid DNA unwinding and binding dynamics to an oligonucleotide probe as functions of ionic strength, crowding agent concentration, and crowding agent species using single-molecule CLiC microscopy. We demonstrate increased probe-plasmid interaction over time with increasing concentration of 8 kDa polyethylene glycol (PEG), a crowding agent. We show decreased probe-plasmid interactions as ionic strength is increased without crowding. However, when crowding is introduced via 10% 8 kDa PEG, interactions between plasmids and oligos are enhanced. This is beyond what is expected for normal in vitro conditions, and may be a critically important, but as of yet unknown, factor in DNAs proper biological function in vivo. Our results show that crowding has a strong effect on the initial concentration of unwound plasmids. In the dilute conditions used in these experiments, crowding does not impact probe-plasmid interactions once the site is unwound.

biophysics↗