A5020195797- Circadian rhythm and melatonin
- Enzyme function and inhibition
- Photoreceptor and optogenetics research
- Genetics, Aging, and Longevity in Model Organisms
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Neuroendocrine regulation and behavior
- Endoplasmic Reticulum Stress and Disease
- Multiple Myeloma Research and Treatments
- Genetics, Bioinformatics, and Biomedical Research
- Ubiquitin and proteasome pathways
- Tryptophan and brain disorders
- Lipid Membrane Structure and Behavior
- Protein Degradation and Inhibitors
- Adipose Tissue and Metabolism
- Protein Structure and Dynamics
- Heat shock proteins research
MRC Laboratory of Molecular Biology
2023-2025
The Francis Crick Institute
2023
University of York
2020-2021
GlaxoSmithKline (United Kingdom)
2020
Abstract Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive folding macromolecular interactions 1 . Reciprocally, macromolecules restrict the movement of ‘structured’ molecules within their hydration layers, reducing available ‘free’ bulk therefore total thermodynamic potential energy water, or potential. Here, concentrated solutions such as cytosol, we found that modest changes in temperature greatly affect...
The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian feedback. Not all rhythms depend on CRY proteins, however, the promiscuous interactors that also regulate many other processes. In cells with chronic deficiency, protein homeostasis is highly perturbed, a basal increase cellular stress activation of key inflammatory signalling pathways. Here, we developed tools to delineate specific effects reduction, rather than better...
Abstract Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and transmission hosts, requiring stringent spatial temporal regulation. Here, we apply kinome-wide gene deletion tagging in Leishmania mexicana promastigotes to define protein kinases with transition roles. Whilst 162 are dispensable, 44 kinase genes refractory likely core required parasite replication. Phenotyping pooled mutants using bar-seq projection pursuit clustering...
Abstract Early mammals were nocturnal until the Cretaceous-Paleogene extinction facilitated their rapid expansion into daytime niches. Diurnality subsequently evolved multiple times, independently, but mechanisms facilitating this switch are unknown. We found that physiological daily temperature shifts oppositely affect circadian clock rhythms in versus diurnal mammals. This occurs through a cell-intrinsic signal inverter, mediated by global differences protein phosphorylation, and effected...
Summary Circadian rhythms result from cell-intrinsic timing mechanisms that impact health and disease 1,2 . To date, however, neural circadian research has largely focused on the hypothalamic circuitry of nocturnal rodents 3 Whether exist in human brain cells is unknown. Here we show bona fide neurons, glia, cerebral organoids, organoid slices (ALI-COs) 4–8 Human are synchronised by physiological cues such as glucocorticoids daily temperature cycles, these temperature-compensated across...
Summary Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and transmission hosts, requiring stringent spatial temporal regulation. Here we applied kinome-wide gene deletion tagging in Leishmania mexicana promastigotes to define protein kinases with transition roles. Whilst 162 were dispensable, 44 kinase genes refractory are likely core required parasite replication. Phenotyping pooled mutants using bar-seq projection pursuit...