A5060445219- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- DNA Repair Mechanisms
- Viral gastroenteritis research and epidemiology
- COVID-19 and healthcare impacts
- Vaccine Coverage and Hesitancy
- Animal Virus Infections Studies
- Biosensors and Analytical Detection
- Autophagy in Disease and Therapy
- Viral Infections and Immunology Research
- Viral Infections and Outbreaks Research
- vaccines and immunoinformatics approaches
- Plant and Fungal Interactions Research
- COVID-19 epidemiological studies
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- interferon and immune responses
- Cancer Genomics and Diagnostics
- Influenza Virus Research Studies
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
The Francis Crick Institute
2020-2025
University of Toronto
2024
ORCID
2022
University College London
2020-2022
University of Leicester
2022
University Hospitals of Leicester NHS Trust
2022
Glenfield Hospital
2022
NIHR Leicester Biomedical Research Centre
2022
University of Cambridge
2022
Cambridge University Hospitals NHS Foundation Trust
2022
Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis macromolecules. The PI3-kinase/Akt signaling pathway induces cell via activation complex 1 target rapamycin (TORC1). Here we show Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear accumulation mature form sterol responsive element binding protein (SREBP1) and expression SREBP genes was blocked by inhibitor rapamycin. We also silencing blocks...
Abstract Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is prospective cohort study of COVID-19 immunity patients with cancer. Here we evaluated 585 following administration two doses BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after were 85% and 59% solid hematological malignancies, respectively. A lower proportion had detectable titers neutralizing antibodies (NAbT) against severe acute...
Abstract Microbial communities are composed of cells varying metabolic capacity, and regularly include auxotrophs that lack essential pathways. Through analysis for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial obtained as part the Earth Microbiome Project (EMP), study auxotrophic–prototrophic interactions self-establishing metabolically cooperating yeast (SeMeCos), we reveal a imprinted mechanism links presence to an increase gains...
Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current disease 2019 (COVID-19) pandemic. Although antibody cross-reactivity with spike glycoproteins (S) diverse coronaviruses, including endemic common cold coronaviruses (HCoVs), has been documented, it remains unclear whether such responses, typically targeting conserved S2 subunit, contribute to protection when induced by infection or through vaccination. Using a mouse model, we...
Macroautophagy is a mechanism employed by eukaryotic cells to recycle non-essential cellular components during starvation, differentiation, and development. Two conjugation reactions related ubiquitination are essential for autophagy: Apg12p Apg5p, Apg8p the lipid phosphatidylethanolamine. These require action of E1-like enzyme, Apg7p, E2-like enzymes, Apg3p Apg10p. InDictyostelium, development induced conditions under which autophagy required survival in yeast plants. We have identified...
Abstract APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when expression is induced during cancer development remains to be defined. Here we show that specific genes upregulated breast ductal carcinoma situ, and preinvasive lung lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx invasive non–small cell (NSCLC) lesions. find APOBEC3B exacerbates DNA replication stress chromosomal...
Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling clinical annotation. Of 357 patients cancer, 118 were SARS-CoV-2 positive, 94 symptomatic 2 died of COVID-19. In this cohort, 83% had S1-reactive antibodies 82% neutralizing against wild type SARS-CoV-2, whereas antibody titers Alpha, Beta Delta variants substantially reduced. levels decreased in 13% patients, remained stable for up to...
The coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2), a global public health challenge. While the efficacy of vaccines against emerging and future virus variants remains unclear, there need for therapeutics. Repurposing existing drugs represents promising potentially rapid opportunity to find novel antivirals SARS-CoV-2. encodes at least nine enzymatic activities that are potential drug targets. Here, we have expressed,...
SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered economies of countries families around the world. Antiviral treatments combat COVID-19 are currently lacking. Remdesivir, only antiviral drug approved treatment can affect severity, but better needed. encodes 16 non-structural proteins (nsp) possess different enzymatic activities with important roles in viral genome replication,...
The COVID-19 pandemic has emerged as the biggest life-threatening disease of this century. Whilst vaccination should provide a long-term solution, is pitted against constant threat mutations in virus rendering current vaccines less effective. Consequently, small molecule antiviral agents would be extremely useful to complement program. causative agent novel coronavirus, SARS-CoV-2, which encodes at least nine enzymatic activities that all have drug targeting potential. papain-like protease...
The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), spread around world with unprecedented health and socio-economic effects for global population. While different vaccines are now being made available, very few antiviral drugs have been approved. main viral protease (nsp5) of SARS-CoV-2 provides an excellent target antivirals, due to its essential conserved function in replication cycle. We expressed, purified developed assays nsp5...
Deubiquitylating enzymes (DUBs) play an essential role in targeted protein degradation and represent emerging therapeutic paradigm cancer. However, their potential pancreatic ductal adenocarcinoma (PDAC) has not been explored. Here, we develop a DUB discovery pipeline, combining activity-based proteomics with loss-of-function genetic screen patient-derived PDAC organoids murine models. This approach identifies USP25 as master regulator of growth maintenance. Genetic pharmacological...
ObjectivesTo investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.MethodsWe performed a case-control study, comparing with singly infected individuals pre-vaccination, matched by gender, age, region timing first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), nucleocapsid (anti-N), live virus microneutralisation (LV-N) pseudovirus (PV-N). Results analysed...
BackgroundThe humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody two doses, is fully understood. The OCTAVE DUO trial aimed determine the value of third vaccinations a wide range patients with primary secondary immunodeficiencies.MethodsOCTAVE-DUO was prospective, open-label, multicentre, randomised, controlled, phase 3 investigating are following dose BNT162b2 or mRNA-1273, NVX-CoV2373 for those...
Computational design of protein-binding proteins is a fundamental capability with broad utility in biomedical research and biotechnology. Recent methods have made strides against some target proteins, but on-demand creation high-affinity binders without multiple rounds experimental testing remains an unsolved challenge. This technical report introduces AlphaProteo, family machine learning models for protein design, details its performance on the de novo binder problem. With we achieve 3- to...
Macroautophagy is the major mechanism that eukaryotes use to recycle cellular components during stressful conditions. We have shown previously Atg12-Atg5 conjugation system, required for autophagosome formation in yeast, necessary Dictyostelium development. A second reaction, Aut7/Atg8 lipidation with phosphatidylethanolamine, as well a protein kinase complex and phosphatidylinositol 3-kinase are also macroautophagy yeast. In this study, we characterize mutations putative discoideum...