Biology subjects

Burridge, C.

Publications and source records attributed to Burridge, C..

4 recordsLinked to original sources

bioRxiv2026

Thermally driven sex reversal reveals divergent sex determination dynamics in wild viviparous reptile populations

Climate change can threaten population viability by disrupting sex ratios in species whose sex is influenced by temperature. While species with sex chromosomes were historically considered immune, in some species, temperatures can override genetic sex determination via sex reversal, leaving them vulnerable to climate-driven sex ratio shifts. The Tasmanian spotted snow skink (Carinacincus ocellatus), a viviparous reptile with an XX/XY system, provides a compelling case study. While laboratory studies demonstrated that extreme thermal conditions induce female-to-male sex reversal (XX males), its occurrence in the wild remains unexplored, limiting our understanding of actual climate impacts. Integrating 23 years of phenotypic and genetic sexing data across two climatically distinct populations, we provide the first evidence of sex reversal in a wild viviparous reptile. XX reversal occurred in both populations, affecting up to 23.5% of XX births in the warmer population, and was associated with colder minimum daily temperatures. Despite high birth rates in some years, sex-reversed adults were rare. We also identified putative XY females, suggesting bidirectional sex reversal and reinforcing the extreme plasticity of reptilian sex determination. Ultimately, sex reversal could act as an evolutionary trap, potentially compromising population viability as climate instability increases.

evolutionary biology↗

bioRxiv2025

Long-range electrostatic forces govern how proteins fold on the ribosome

Protein biosynthesis and folding are tightly intertwined processes regulated by the ribosome and auxiliary factors. Nascent proteins can begin to fold on their parent ribosome but formation of the native state is often inhibited well beyond the emergence of the necessary residues from the exit tunnel. The dominant forces driving this apparent destabilisation have remained unclear. We investigate this here, combining NMR experiments and atomistic simulations of a folded nascent chain on and off the ribosome. While its native structure and internal dynamics remain unaltered, co-translational folding is disfavoured due to intermolecular electrostatic repulsion between the negatively charged ribosome surface and nascent protein. Partially folded intermediates are less destabilised, resulting in their high populations. Specifically, we show that the polypeptides net charge is the dominant factor determining nascent folding thermodynamics, with smaller contributions from charge distribution. Consequently, positively charged proteins can fold on the ribosome without populating stable intermediates. These findings reconcile conflicting observations of previous studies and establish the general physical principles underpinning de novo protein folding.

biophysics↗

bioRxiv2023

Targeting NRP1 with EG00229 induces neurovascular permeability

NRP1 is a therapeutic target for inhibiting vascular endothelial growth factor (VEGF)-induced blood vessel dysfunction. The small molecule EG00229 was designed to inhibit VEGF binding to NRP1 and reduce pathological blood vessel growth. However, it is unknown whether EG00229 could also be used to reduce VEGF164-induced vascular leakage, which often exacerbates ischemic diseases due to VEGF upregulation. Here, we show that prior treatment with EG00229 prevents VEGF164-induced vascular permeability signalling, but, unexpectedly, also find that EG00229 increased rather than inhibited vascular leakage. Thus, EG00229 increased vascular leakage either when added alone or concurrently with VEGF164, both in perfused retinal explants and across primary brain EC monolayers. This EG00229-induced vascular leakage was not an off-target effect, because it relied on endothelial NRP1 expression and NRP1s VEGF164 binding pocket, yet was independent of VEGFR1 and VEGFR2. Moreover, EG00229 activated molecular events typical of VEGF164-induced paracellular permeability, including p38 MAP kinase (p38) and SRC family kinase (SFK) phosphorylation as well as CDH5 rearrangement in endothelial junctions. Investigating EG00229-induced signalling therefore helps elucidate NRP1-dependent mechanisms of paracellular permeability induction and might help identifying new approaches to modulate the neurovascular barrier.

physiology↗

bioRxiv2020

Optimal design of adaptively sampled NMR experiments for measurement of methyl group dynamics with application to a ribosome-nascent chain complex

NMR measurements of cross-correlated nuclear spin relaxation provide powerful probes of polypeptide dynamics and rotational diffusion, free from contributions due to chemical exchange or interactions with external spins. Here, we report on the development of a sensitivity-optimized pulse sequence for the measurement of cross-correlated relaxation in methyl spin systems by analysis of the differential relaxation of transitions within the 13C multiplet. We describe the application of optimal design theory to implement a real-time on-the-fly adaptive sampling scheme that maximizes the accuracy of the measured rate constants. The increase in sensitivity obtained using this approach enables, for the first time, quantitative measurements of rotational diffusion within folded states of translationally-arrested ribosome-nascent chain complexes of the FLN5 filamin domain, and can be used to place strong limits on interactions between the domain and the ribosome surface.

biophysics↗