Thomas Christott
A5033474962- SARS-CoV-2 and COVID-19 Research
- Protein Degradation and Inhibitors
- COVID-19 Clinical Research Studies
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- COVID-19 epidemiological studies
- COVID-19 and healthcare impacts
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Plant nutrient uptake and metabolism
- Microtubule and mitosis dynamics
- Acute Myeloid Leukemia Research
- Vaccine Coverage and Hesitancy
- Polysaccharides and Plant Cell Walls
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Infection Control and Ventilation
- SARS-CoV-2 detection and testing
- Multiple Myeloma Research and Treatments
- Galectins and Cancer Biology
- Viral Infections and Immunology Research
- Bacillus and Francisella bacterial research
- Click Chemistry and Applications
University of Oxford
2018-2024
University of Manchester
2021
Sci-Tech Daresbury
2021
Office for National Statistics
2020
Genomics England
2018-2019
Genomics (United Kingdom)
2019
<h2>Summary</h2><h3>Background</h3> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in 2020. Testing is crucial for mitigating public health and economic effects. Serology considered key to population-level surveillance potentially individual-level risk assessment. However, immunoassay performance not been compared on large, identical sample sets. We aimed investigate the of four high-throughput commercial SARS-CoV-2 antibody immunoassays novel...
Abstract We report that in a cohort of 45,965 adults, who were receiving either the ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines, those had no prior infection with SARS-CoV-2, seroconversion rates and quantitative antibody levels after single dose lower older individuals, especially aged >60 years. Two vaccine doses achieved high responses across all ages. Antibody increased more slowly to compared BNT162b2, but waned following individuals. In descriptive latent class models, we identified...
We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR immunoassays IgG antibodies. 1128/10,034 (11.2%) had evidence of some time. Using questionnaire data provided on potential risk-factors, with confirmed household contact were greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45–6.72]). Higher rates seen in working Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99–3.08])....
Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration protection a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG correlates doses ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in United Kingdom general population. 222,493 individuals, found significant boosting by both all ages using different...
Understanding the trajectory, duration, and determinants of antibody responses after SARS-CoV-2 infection can inform subsequent protection risk reinfection, however large-scale representative studies are limited. Here we estimated response in general population using data from 7,256 United Kingdom COVID-19 survey participants who had positive swab PCR tests 26-April-2020 to 14-June-2021. A latent class model classified 24% as 'non-responders' not developing anti-spike antibodies, were older,...
Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have potential to evade natural immunity.
Following primary SARS-CoV-2 vaccination, whether boosters or breakthrough infections provide greater protection against infection is incompletely understood. Here we investigated antibody correlates of new Omicron BA.4/5 (re-)infections and anti-spike IgG trajectories after a third/booster vaccination following second in 154,149 adults ≥18 y from the United Kingdom general population. Higher levels were associated with increased higher at any given level than boosters. Breakthrough...
YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation these modified lysine-binding has been linked to the onset and progression cancers. We herein report discovery characterisation first small-molecule chemical probe, SGC-iMLLT, for YD MLLT1 (ENL/YEATS1) MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent selective inhibitor MLLT1/3-histone interactions. Excellent selectivity over other human (YEATS2/4) bromodomains was observed....
Eleven-nineteen leukemia (ENL) contains an epigenetic reader domain (YEATS domain) that recognizes lysine acylation on histone 3 and facilitates transcription initiation elongation through its interactions with the super complex (SEC) methyl transferase DOT1L. Although it has been known for role as a fusion protein in mixed lineage (MLL), overexpression of native ENL, thus dysregulation downstream genes acute myeloid (AML), recently implicated driver disease is reliant activity YEATS domain....
Modifications of histone tails, including lysine/arginine methylation, provide the basis a "chromatin or code". Proteins that contain "reader" domains can bind to these modifications and form specific effector complexes, which ultimately mediate chromatin function. The spindlin1 (SPIN1) protein contains three Tudor methyllysine/arginine reader was identified as putative oncogene transcriptional coactivator. Here we report SPIN1 chemical probe inhibitor with low nanomolar in vitro activity,...
"Classic" symptoms (cough, fever, loss of taste/smell) prompt severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing in the United Kingdom. Studies have assessed ability different to identify infection, but few compared over time (reflecting variants) and by vaccination status.
Abstract Population-representative estimates of SARS-CoV-2 infection prevalence and antibody levels in specific geographic areas at different time points are needed to optimise policy responses. However, even population-wide surveys potentially impacted by biases arising from differences participation rates across key groups. Here, we used spatio-temporal regression post-stratification models UK’s national COVID-19 Infection Survey (CIS) obtain representative PCR positivity (6,496,052 tests)...
By screening an epigenetic compound library, we identified that UNC0638, a highly potent inhibitor of the histone methyltransferases G9a and GLP, was weak SPIN1 (spindlin 1), methyllysine reader protein. Our optimization this hit resulted in discovery potent, selective, cell-active inhibitor, 3 (MS31). Compound potently inhibited binding trimethyllysine-containing peptides to SPIN1, displayed high affinity, selective for over other readers writers, directly engaged cells, not toxic...
YEATS-domain-containing MLLT1 is an acetyl/acyl-lysine reader domain, which structurally distinct from well-studied bromodomains and has been strongly associated in development of cancer. Here, we characterized piperazine-urea derivatives as mimetic moiety for MLLT1. Crystal structures revealed interaction mechanisms this chemotype compared to the recently described benzimidazole-amide based inhibitors, exploiting different binding pockets within protein. Thus, scaffold offers alternative...
A series of small-molecule YEATS4 binders have been discovered as part an ongoing research effort to generate high-quality probe molecules for emerging and/or challenging epigenetic targets. Analogues such 4d and 4e demonstrate excellent potency selectivity binding versus YEATS1,2,3 exhibit good physical properties in vitro safety profiles. new X-ray crystal structure confirms direct this chemical at the lysine acetylation recognition site YEATS domain. Multiple analogues engage with...
Abstract Background Personal protective equipment (PPE) and social distancing are designed to mitigate risk of occupational SARS-CoV-2 infection in hospitals. Why healthcare workers nevertheless remain at increased is uncertain. Methods We conducted voluntary Covid-19 testing programmes for symptomatic asymptomatic staff a UK teaching hospital using nasopharyngeal PCR immunoassays IgG antibodies. A positive result by either modality determined composite outcome. Risk-factors were...
Abstract Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out in many settings, there is a need for evidence to underpin optimum deployment, aiming maximise global population immunity. We evaluate whether single vaccination individuals who have already been infected generates similar initial subsequent antibody responses two vaccinations those without prior infection. compared anti-spike IgG after ChAdOx1, BNT162b2, or mRNA-1273 vaccines the COVID-19 Infection...
Abstract The physiological effects of vaccination against SARS-CoV-2 (COVID-19) are well documented, yet the behavioural not known. Risk compensation suggests that gains in personal safety, as a result vaccination, offset by increases risky behaviour, such socialising, commuting and working outside home. This is potentially important because transmission driven contacts, which could be amplified vaccine-related risk compensation. Here, we show behaviours were overall unrelated to...
<p>YEATS domain (YD) containing proteins are an emerging</p> <p>class of epigenetic targets in drug discovery. Dysregulation these modified lysine binding has been linked to the onset and progression cancers. We herein report discovery characterisation first small molecule chemical probe, SGC-iMLLT, for YD MLLT1 (ENL/YEATS1) MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent selective inhibitor MLLT1/3 -histone interactions. Excellent selectivity over other human (YEATS2/4)...
The S100 protein family functions as protein–protein interaction adaptors regulated by Ca2+ binding. Formation of various complexes plays a central role in cell functions, from calcium homeostasis to signaling, and is implicated growth, migration, tumorigenesis. We established suite biochemical cellular assays for small molecule screening based on known interactions. From 25 human proteins, we focused our attention S100A4 because its well-established cancer progression metastasizes...
Abstract YEATS‐Domänen(YD)‐enthaltende Proteine sind eine neue Klasse epigenetischer Zielstrukturen für die Wirkstoffentwicklung. Die YD‐enthaltenden MLLT1 (ENL/YEATS1) und MLLT3 (AF9/MLLT3) oft in Krebs dereguliert wurden daher als potentielle Therapieansätze diskutiert. Wir berichten hier Entwicklung Charakterisierung des ersten niedermolekularen Inhibitors der YD MLLT3, SGC‐iMLLT . Er ist ein potenter selektiver Inhibitor MLLT1/3‐Histon‐Interaktion zeichnet sich durch exzellente...
YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation these modified lysine binding has been linked to the onset and progression cancers. We herein report discovery characterisation first small molecule chemical probe, SGC-iMLLT, for YD MLLT1 (ENL/YEATS1) MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent selective inhibitor MLLT1/3 -histone interactions. Excellent selectivity over other human (YEATS2/4) bromodomains was observed....