A5015799851- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Respiratory viral infections research
- Trypanosoma species research and implications
- interferon and immune responses
- Biochemical and Molecular Research
- Research on Leishmaniasis Studies
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 detection and testing
- Drug Transport and Resistance Mechanisms
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- COVID-19 Impact on Reproduction
- Biosensors and Analytical Detection
- Viral-associated cancers and disorders
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Obesity, Physical Activity, Diet
- Advanced X-ray and CT Imaging
- Signaling Pathways in Disease
- Long-Term Effects of COVID-19
- Inflammasome and immune disorders
- Medical Imaging Techniques and Applications
- Coffee research and impacts
University of Cambridge
2020-2025
Addenbrooke's Hospital
2022
Cambridge School
2022
King Abdullah University of Science and Technology
2022
Erasmus University Rotterdam
2021
Erasmus MC
2021
University of Dundee
2014-2019
Czech Academy of Sciences
2019
Wellcome Centre for Anti-Infectives Research
2018-2019
University of Glasgow
2011
Abstract Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2) 1 , could represent a new chemoprophylactic approach for COVID-19 that complements vaccination 2,3 . However, the mechanisms control expression of ACE2 remain unclear. Here we show farnesoid X receptor (FXR) is direct regulator transcription in several tissues affected COVID-19, including gastrointestinal and respiratory systems. We then use over-the-counter compound...
Inherited genetic factors can influence the severity of COVID-19, but molecular explanation underpinning a association is often unclear. Intracellular antiviral defenses inhibit replication viruses and reduce disease severity. To better understand relevant to we used interferon-stimulated gene (ISG) expression screening reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show common...
The spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding host receptors including ACE2. An alternate entry receptor for the virus was recently proposed be basigin/CD147. These early studies have already prompted a clinical trial and multiple published hypotheses speculating on role this in infection pathogenesis. Here, we report that are unable find evidence supporting basigin as putative receptor. Recombinant forms do not interact with...
HPLC analysis of 20 commercial espresso coffees revealed 6-fold differences in caffeine levels, a 17-fold range caffeoylquinic acid contents, and 4-fold the : ratio. These variations reflect batch-to-batch bean composition, possible blending arabica with robusta beans, as well roasting grinding procedures, but predominant factor is likely to be amount beans used coffee-making/barista processes. The most single was 322 mg further three contained >200 mg, exceeding 200 day−1 upper limit...
The outcome of infection is dependent on the ability viruses to manipulate infected cell evade immunity, and immune response overcome this evasion. Understanding process key understanding pathogenesis, genetic risk factors, both natural vaccine-induced immunity. SARS-CoV-2 antagonises innate interferon response, but whether it manipulates cellular immunity unclear. An unbiased proteomic analysis determined how surface protein expression altered SARS-CoV-2-infected lung epithelial cells,...
Efforts to define serological correlates of protection against COVID-19 have been hampered by the lack a simple, scalable, standardised assay for SARS-CoV-2 infection and antibody neutralisation. Plaque assays remain gold standard, but are impractical high-throughput screening. In this study, we show that expression viral proteases may be used quantitate infected cells. Our exploit cleavage specific oligopeptide linkers, leading activation cell-based optical biosensors. First, characterise...
The interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead Disease 2019 (COVID-19). spike protein is largest structural component of mediates essential for infection, including with primary angiotensin-converting enzyme (ACE2) receptor. We performed two independent cell-based systematic screens determine whether there are additional proteins by which SARS-CoV-2 can interact cells. discovered...
We describe a single-step centrifugal elutriation method to produce synchronous Gap1 (G1)-phase procyclic trypanosomes at scale amenable for proteomic analysis of the cell cycle. Using ten-plex tandem mass tag (TMT) labeling and spectrometry (MS)-based proteomics technology, expression levels 5325 proteins were quantified across cycle in this parasite. Of these, 384 classified as cell-cycle regulated subdivided into nine clusters with distinct temporal regulation. These groups included many...
Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the leading cause of mortality in HIV infection. KSHV reactivation from latent- to lytic-stage infection initiates a cascade viral gene expression. Here we show how these changes remodel host cell proteome enable replication. By undertaking systematic unbiased analysis endothelial following reactivation, quantify >7,000 cellular proteins 71 provide temporal profile protein during course lytic Lytic induces >2-fold...
Abstract The TMPRSS2 cell surface protease is used by a broad range of respiratory viruses to facilitate entry into target cells. Together with ACE2, represents key factor for SARS-CoV-2 infection, as mediates cleavage viral spike protein, enabling direct fusion the envelope host membrane. Since start COVID-19 pandemic, has gained attention therapeutic inhibitors which would inhibit but little known about regulation, particularly in types physiologically relevant infection. Here, we...
<ns4:p><ns4:bold>Background</ns4:bold>: Cellular proteins vary significantly in both abundance and turnover rates. These parameters depend upon their rates of synthesis degradation it is useful to have access data on protein when, for example, designing genetic knock-down experiments or assessing the potential usefulness covalent enzyme inhibitors. Little known about nature regulation <ns4:italic>Trypanosoma brucei</ns4:italic>, etiological agent human animal African...
Trypanosoma cruzi, the etiological agent of Chagas' disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), classical infective stage, interact with extracellular matrix (ECM), an obligatory step before invasion almost all mammalian cells different tissues. Here we have characterized proteome and phosphoproteome upon interaction ECM (MTy) data are available via ProteomeXchange identifier PXD010970. Proteins involved...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases SARS-CoV-2 vitro. HCMV is a common herpesvirus carried by 40%-100% population, which can reactivate lung under inflammatory conditions, such as those resulting from infection. We show both endothelial...
A disproportionate number of predicted proteins from the genome sequence protozoan parasite Trypanosoma brucei, an important human and animal pathogen, are hypothetical unknown function. This paper describes a protein correlation profiling mass spectrometry approach, using two size exclusion one ion exchange chromatography systems, to derive sets complexes in this organism by hierarchical clustering machine learning methods. These hypothesis-generating proteomic data provided open access...
There are limited effective prophylactic/early treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral entry requires spike protein binding to the angiotensin-converting enzyme-2 receptor and cleavage by transmembrane serine protease (TMPRSS2), a cell surface protease. Targeting of TMPRSS2 either androgen blockade or direct inhibition is in clinical trials early SARS-CoV-2
Animal African Trypanosomosis (AAT) presents a severe problem for agricultural development in sub-Saharan Africa. It is caused by several trypanosome species and current means of diagnosis are expensive impractical field use. Our aim was to discover antigens the detection antibodies Trypanosoma congolense, one main causative agents AAT. We took proteomic approach identify potential immunodiagnostic parasite protein antigens. One hundred thirteen proteins were identified which selectively...
Summary The interactions between severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead COVID-19. spike protein is largest structural component of mediates essential for infection, including with primary ACE2 receptor. We performed two independent cell-based systematic screens determine whether there are additional proteins by which SARS-CoV-2 can interact cells. discovered in addition ACE2, expression...
Abstract Cell autonomous antiviral defenses can inhibit the replication of viruses and reduce transmission disease severity. To better understand response to SARS-CoV-2, we used interferon-stimulated gene (ISG) expression screening reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show while some people express a prenylated OAS1 variant, is membrane-associated blocks SARS-CoV-2 infection, other cytosolic, nonprenylated variant which does not detect (determined by...
BackgroundCigarette smoking has many serious negative health consequences. The relationship between and SARS-CoV-2 infection is controversial, specifically whether smokers are at increased risk of infection. We investigated the impact cigarette smoke on ACE2 isoform expression in differentiated primary human bronchial epithelial cells air-liquid-interface (ALI). assessed response to CSE therapeutics reported modulate ACE2. exposed ALI cultures extract (CSE) then infected them with...
Quantitative proteomics is able to provide a comprehensive, unbiased description of changes cells caused by viral infection, but interpretation may be complicated differential in infected and uninfected 'bystander' cells, or the use non-physiological cellular models.
Abstract Efforts to define serological correlates of protection against COVID-19 have been hampered by the lack a simple, scalable, standardised assay for SARS-CoV-2 infection and antibody neutralisation. Plaque assays remain gold standard, but are impractical high-throughput screening. In this study, we show that expression viral proteases may be used quantitate infected cells. Our exploit cleavage specific oligopeptide linkers, leading activation cell-based optical biosensors. First,...
Abstract Prevention of SARS-CoV-2 entry in cells through the modulation viral host receptors, such as ACE2, could represent a new therapeutic approach complementing vaccination. However, mechanisms controlling ACE2 expression remain elusive. Here, we identify farnesoid X receptor (FXR) direct regulator transcription multiple COVID19-affected tissues, including gastrointestinal and respiratory systems. We demonstrate that FXR antagonists, over-the-counter compound z-guggulsterone (ZGG)...
Abstract Background There are limited effective prophylactic treatments for SARS-CoV-2 infection, and early treatment options. Viral cell entry requires spike protein binding to the ACE2 receptor cleavage by TMPRSS2, a surface serine protease. Targeting of TMPRSS2 either androgen blockade or direct inhibition is already in clinical trials infection. Methods The likely initial cells ciliated upper airway. We therefore used differentiated primary human airway epithelial maintained at...