Biology subjects

Richards, H.

Publications and source records attributed to Richards, H..

5 recordsLinked to original sources

bioRxiv2026

Gut Microbiota Signatures of Brain and Peripheral gamma-amino butyric acid (GABA) in Healthy Adult Males

Gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the mature human nervous system, plays a central role in neurodevelopment, emotion regulation, and sensory processing. Many psychiatric drugs act on the GABAergic system, highlighting its importance for healthy brain function. Individual differences in brain and circulating GABA levels have traditionally been attributed to genetic variation. However, several gut bacteria produce neuroactive compounds, including GABA, raising the possibility that microbial variation influences peripheral and central GABA levels and related measures in humans. This relationship remains largely unexplored. In a cross-sectional study of 251 healthy adults, we investigated associations between gut microbiota composition, central and peripheral GABA, and associated features. Brain GABA was quantified using magnetic resonance spectroscopy, blood GABA using enzyme-linked immunosorbent assays, and gut microbiota profiles using absolute and relative abundance measures derived from Flow Cytometry Fluorescent In Situ Hybridisation and 16S rRNA gene sequencing. Motor cortex GABA+ levels were positively associated with greater numbers of Bacteroides/Prevotella bacteria. A similar association was observed for blood GABA, which was additionally associated with greater numbers of lactic acid bacteria, Eubacterium rectale/Clostridium coccoides, and Clostridium histolyticum groups, and with predicted microbial gene pathways involved in GABA, propionate, and butyrate biosynthesis. No association was observed between brain and blood GABA concentrations. These findings provide new evidence for relationships between gut bacterial groups and central and peripheral GABA pools, supporting future longitudinal studies of causal links between gut microbiota and host GABA levels, as well as the potential for future intervention studies to influence GABAergic processing.

neuroscience↗

bioRxiv2025

OGDHL regulates nucleotide metabolism, tumor growth, and neuroendocrine marker expression in prostate cancer

As cancer cells evade therapeutic pressure and adopt alternate lineage identities not commonly observed in the tissue of origin, they likely adopt alternate metabolic programs to support their evolving demands. Targeting these alternative metabolic programs in distinct molecular subtypes of aggressive prostate cancer may lead to new therapeutic approaches to combat treatment-resistance. We identify the poorly studied metabolic enzyme Oxoglutarate Dehydrogenase-Like (OGDHL), named for its structural similarity to the tricarboxylic acid (TCA) cycle enzyme Oxoglutarate Dehydrogenase (OGDH), as an unexpected regulator of tumor growth, treatment-induced lineage plasticity, and DNA Damage in prostate cancer. While OGDHL has been described as a tumor-suppressor in various cancers, we find that its loss impairs prostate cancer cell proliferation and tumor formation. Loss of OGDHL profoundly alters Androgen Receptor inhibition-induced plasticity, including suppressing the neuroendocrine markers DLL3 and HES6, induces accumulation of the DNA damage response marker {gamma}H2AX, and reduces nucleotide synthesis. Our data suggest that OGDHL has minimal impact on TCA cycle activity, and that mitochondrial localization is not required for its regulation of prostate cancer plasticity and nucleotide metabolism. Finally, we demonstrate that OGDHL expression is tightly correlated with neuroendocrine differentiation in clinical prostate cancer. These findings underscore the importance of investigating poorly characterized metabolic genes as potential regulators of distinct molecular subtypes of aggressive cancer.

cancer biology↗

bioRxiv2025

Evolutionary potential of the Escherichia coli antimutator ΔnudJ is reduced via altered mutational spectrum

The rate of spontaneous mutation is a key factor in determining the capacity of a population to adapt to a novel environment, for example a bacterial population exposed to antibiotics. Genetic and environmental factors controlling the mutation rate commonly also cause shifts in the relative rates of different mutational classes, i.e. the spectrum of spontaneous mutations. When the mutational spectrum is altered, the relatively enriched and depleted mutations may differ in their fitness effects. Here we aim to explore how a reduced mutation rate and altered mutational spectrum can contribute to adaptation in Escherichia coli. We measure mutation rates across a set of Nudix hydrolase deletants, finding multiple strains with an antimutator phenotype. We focus on the antimutator {Delta}nudJ which can cause a 6-fold mutation rate reduction relative to the wildtype with an altered mutational spectrum. Not only does nudJ deletion reduce the probability of antibiotic resistance arising but, in the case of rifampicin, the accessible resistance mutations under this altered mutation spectrum have greater fitness costs. While this effect is, so far, specific to this drug, it opens up the possibility of reducing the likelihood of resistance mutations establishing through simultaneous modification of mutation rate and spectrum. The identification and characterisation of antimutator alleles such as {Delta}nudJ provides potential targets for antievolution drugs which could be applied during antibiotic treatment to inhibit NudJ activity. Such an approach could suppress spontaneous resistance evolution both through fewer resistance mutations and by limiting access to the fittest mutations.

evolutionary biology↗

bioRxiv2024

Antarctic geothermal soils exhibit an absence of regional habitat generalist microorganisms

Active geothermal systems are relatively rare in Antarctica and represent metaphorical islands ideal to study microbial dispersal. In this study, we tested the macroecological concept that high dispersal rates result in communities being dominated by either habitat generalists or specialists by investigating the microbial communities on four geographically separated geothermal sites on three Antarctic volcanoes (Mts. Erebus, Melbourne and Rittman). We found that the microbial communities at higher temperature (max 65{square}) sites (Tramway Ridge on Erebus and Rittmann) were unique from each other and were dominated by a variety of novel Archaea from class Nitrososphaeria, while lower temperature (max 50{square}) sites (Western Crater on Erebus and Melbourne) had characteristically mesophilic communities (Planctomycetes, Acidobacteriota, etc) that were highly similar. We found that 97% of the detected microbial taxa were regional habitat specialists, with no generalists, with community assembly driven by high dispersal rates and drift (25 and 30% of community assembly, respectively), not environmental selection. Our results indicate that for microbial communities experiencing high dispersal rates between isolated communities, habitat specialists may tend to out-compete habitat generalists.

microbiology↗

bioRxiv2018

Opposing effects of population density and stress on Escherichia coli mutation rate

Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis - SIM) and decrease at high population density (density-associated mutation-rate plasticity - DAMP). We hypothesised that these two forms of mutation rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli bacteria in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM result in a mutation rate minimum at intermediate nutrient levels (which can support 7x108 cells ml-1). These findings demonstrate a strikingly close and nuanced relationship of ecological factors - stress and population density - with mutation, the fuel of all evolution.

evolutionary biology↗