Thomas S. Blacker
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View article: A mismatch in enzyme-redox partnerships underlies divergent cytochrome P450 activities between human hepatocytes and microsomes
A mismatch in enzyme-redox partnerships underlies divergent cytochrome P450 activities between human hepatocytes and microsomes Open
NADPH-P450 oxidoreductase (POR) is the accepted redox-partner for drug-metabolising cytochrome P450s (CYPs) over NADH-cytochrome b 5 reductase (Cyt b 5 R). Accordingly, POR-centric NADPH-supplemented human liver microsomes (HLM) and recomb…
View article: Targeting Lysosomal pH Restores Mitochondrial Quality Control in GBA1-Mutant Parkinson’s Disease
Targeting Lysosomal pH Restores Mitochondrial Quality Control in GBA1-Mutant Parkinson’s Disease Open
Background Heterozygous mutations in the Glucocerebrosidase gene (GBA1), which encodes the lysosomal enzyme β-glucocerebrosidase (GCase), are a genetic risk factor for Parkinson’s disease (PD), characterised by lysosomal dysfunction. The p…
View article: Targeting Lysosomal pH Restores Mitochondrial Quality Control in GBA1-Mutant Parkinson’s Disease
Targeting Lysosomal pH Restores Mitochondrial Quality Control in GBA1-Mutant Parkinson’s Disease Open
Heterozygous mutations in the Glucocerebrosidase gene ( GBA1 ), encoding the lysosomal hydrolase β-glucocerebrosidase (GCase), are a genetic risk factor for Parkinson’s disease (PD). To explore the pathophysiological consequences of these …
View article: Redox‐dependent binding and conformational equilibria govern the fluorescence decay of <scp>NAD</scp> (P)H in living cells
Redox‐dependent binding and conformational equilibria govern the fluorescence decay of <span>NAD</span> (P)H in living cells Open
When probed in living systems using fluorescence lifetime imaging microscopy (FLIM), the emission from reduced nicotinamide adenine dinucleotide (NADH) and its phosphorylated form NADPH have shown promise as sensitive intrinsic reporters o…
View article: Pathological mutation in SMN impairs modulation of GAR1 phase separation linking condensate dysfunction to Spinal Muscular Atrophy
Pathological mutation in SMN impairs modulation of GAR1 phase separation linking condensate dysfunction to Spinal Muscular Atrophy Open
Summary Pathological mutations in liquid-liquid phase separation (LLPS) scaffold proteins have been linked to biomolecular condensate dysfunction in neurodegenerative diseases, while the possible impact of client protein mutations remains …
View article: Redox-dependent binding and conformational equilibria govern the fluorescence decay of NAD(P)H in living cells
Redox-dependent binding and conformational equilibria govern the fluorescence decay of NAD(P)H in living cells Open
When probed using fluorescence lifetime imaging microscopy (FLIM), the emission from reduced nicotinamide adenine dinucleotide (NADH) and its phosphorylated form NADPH have shown promise as sensitive intrinsic reporters of metabolism in li…
View article: Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea
Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea Open
In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along a proximal-to-distal long (tonotopic) axis. Acquisition of unique …
View article: Author response: Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea
Author response: Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea Open
View article: Nrf2 regulates glucose uptake and metabolism in neurons and astrocytes
Nrf2 regulates glucose uptake and metabolism in neurons and astrocytes Open
View article: NAD(P)H binding configurations revealed by time-resolved fluorescence and two-photon absorption
NAD(P)H binding configurations revealed by time-resolved fluorescence and two-photon absorption Open
View article: Crosstalk between glucose metabolism and morphogen signalling specifies tonotopic identity in developing hair cells
Crosstalk between glucose metabolism and morphogen signalling specifies tonotopic identity in developing hair cells Open
In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along the proximal-to-distal long (tonotopic) axis. Acquisition of frequ…
View article: Cellular localisation of structurally diverse diphenylacetylene fluorophores
Cellular localisation of structurally diverse diphenylacetylene fluorophores Open
The cellular localisation of diphenylacetylene fluorophores can be influenced by modifying their structure, modulating lipophilicity and incorporating ionisable groups.
View article: Multiphoton NAD(P)H FLIM reveals metabolic changes in individual cell types of the intact cochlea upon sensorineural hearing loss
Multiphoton NAD(P)H FLIM reveals metabolic changes in individual cell types of the intact cochlea upon sensorineural hearing loss Open
An increasing volume of data suggests that changes in cellular metabolism have a major impact on the health of tissues and organs, including in the auditory system where metabolic alterations are implicated in both age-related and noise-in…
View article: CCDC 1854354: Experimental Crystal Structure Determination
CCDC 1854354: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism
CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism Open
View article: Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells
Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells Open
View article: Polarized Two-Photon Absorption and Heterogeneous Fluorescence Dynamics in NAD(P)H
Polarized Two-Photon Absorption and Heterogeneous Fluorescence Dynamics in NAD(P)H Open
Two-photon absorption (2PA) finds widespread application in biological systems, which frequently exhibit heterogeneous fluorescence decay dynamics corresponding to multiple species or environments. By combining polarized 2PA with time-reso…
View article: CHCHD4 regulates a proliferation-EMT switch in tumour cells, through respiratory complex I mediated metabolism
CHCHD4 regulates a proliferation-EMT switch in tumour cells, through respiratory complex I mediated metabolism Open
BACKGROUND Mitochondrial metabolism involves oxidative phosphorylation (OXPHOS) via the respiratory chain and is required for the maintenance of tumour cell proliferation and regulation of epithelial–mesenchymal transition (EMT)-related ph…
View article: Photoactivated cell-killing involving a low molecular weight, donor–acceptor diphenylacetylene
Photoactivated cell-killing involving a low molecular weight, donor–acceptor diphenylacetylene Open
Drug-like, donor–acceptor diphenylacetylenes cause efficient cell death upon photoactivation and hence have potential phototherapeutic applications.
View article: Time-resolved stimulated emission depletion and energy transfer dynamics in two-photon excited EGFP
Time-resolved stimulated emission depletion and energy transfer dynamics in two-photon excited EGFP Open
Time and polarization-resolved stimulated emission depletion (STED) measurements are used to investigate excited state evolution following the two-photon excitation of enhanced green fluorescent protein (EGFP). We employ a new approach for…
View article: Polarized two-photon photoselection in EGFP: Theory and experiment
Polarized two-photon photoselection in EGFP: Theory and experiment Open
In this work, we present a complete theoretical description of the excited state order created by two-photon photoselection from an isotropic ground state; this encompasses both the conventionally measured quadrupolar (K = 2) and the “hidd…
View article: NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with Glycolysis in Cells with Mitochondrial Dysfunction
NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with Glycolysis in Cells with Mitochondrial Dysfunction Open
View article: Assessment of Cellular Redox State Using NAD(P)H Fluorescence Intensity and Lifetime
Assessment of Cellular Redox State Using NAD(P)H Fluorescence Intensity and Lifetime Open
NADH and NADPH are redox cofactors, primarily involved in catabolic and anabolic metabolic processes respectively. In addition, NADPH plays an important role in cellular antioxidant defence. In live cells and tissues, the intensity of thei…
View article: Investigating State Restriction in Fluorescent Protein FRET Using Time-Resolved Fluorescence and Anisotropy
Investigating State Restriction in Fluorescent Protein FRET Using Time-Resolved Fluorescence and Anisotropy Open
Most fluorescent proteins exhibit multiexponential fluorescence decays, indicating a heterogeneous excited state population. FRET between fluorescent proteins should therefore involve multiple energy transfer pathways. We recently demonstr…
View article: Investigating mitochondrial redox state using NADH and NADPH autofluorescence
Investigating mitochondrial redox state using NADH and NADPH autofluorescence Open
The redox states of the NAD and NADP pyridine nucleotide pools play critical roles in defining the activity of energy producing pathways, in driving oxidative stress and in maintaining antioxidant defences. Broadly speaking, NAD is primari…
View article: The mitochondrial calcium uniporter regulates breast cancer progression via <scp>HIF</scp> ‐1α
The mitochondrial calcium uniporter regulates breast cancer progression via <span>HIF</span> ‐1α Open
View article: Heterogeneity and restricted state selection in FRET with fluorescent proteins
Heterogeneity and restricted state selection in FRET with fluorescent proteins Open
Most fluorescent proteins exhibit multi-exponential fluorescence decays, indicating the presence of a heterogeneous excited state population. In the analysis of FRET to and between fluorescent proteins, it is often convenient to assume tha…
View article: Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure
Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure Open