A5041312518- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Virus-based gene therapy research
- Crime, Illicit Activities, and Governance
- Malaria Research and Control
- Probiotics and Fermented Foods
- Oral microbiology and periodontitis research
- CAR-T cell therapy research
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Cancer-related Molecular Pathways
- Tissue Engineering and Regenerative Medicine
- Zoonotic diseases and public health
- Income, Poverty, and Inequality
- Animal Virus Infections Studies
- Cardiac Fibrosis and Remodeling
- Endodontics and Root Canal Treatments
- Library Science and Information Systems
- Posttraumatic Stress Disorder Research
- Kruppel-like factors research
- RNA Interference and Gene Delivery
- Cybercrime and Law Enforcement Studies
- Chemical Synthesis and Analysis
- RNA modifications and cancer
- Mitochondrial Function and Pathology
MRC Toxicology Unit
2012-2024
University of Leicester
2012-2022
University of Cambridge
2018-2021
Medical Research Council
2014-2019
Genomics (United Kingdom)
2017
Unilever (United Kingdom)
1995
University of Utah
1982
Cole Engineering Services (United States)
1926
Kodak (United States)
1926
Targeting parasite's protein kinase Malaria elimination goals are constantly eroded by the challenge of emerging drug and insecticide resistance. Alam et al. have taken established targets—CLK kinases involved in regulation RNA splicing—and investigated how inhibition enzymes blocks completion its complex life cycle. They identified an inhibitor CLK that was 100-fold less active against most closely related human effective at clearing rodent malaria parasites. Not only does this compound...
A novel mechanism for antagonism of the human chemokine receptors CCR4 and CCR5 has been discovered with a series small-molecule compounds that seems to interact an allosteric, intracellular site on receptor. The existence this is supported by observations: 1) access these antagonists required their activity; 2) specific, saturable binding radiolabeled antagonist requires presence CCR4; 3) through engineering receptor chimeras reciprocal transfer C-terminal domains between CCR5, compound...
Abstract The mammalian target of rapamycin (mTOR) is a critical regulator cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities mTOR control protein synthesis machinery. This achieved, in part, via co-ordinated regulation mRNAs that contain terminal oligopyrimidine tract (TOP) at their 5′ends, although mechanisms by which this occurs are still unclear. We used RNA-binding (RBP) capture to identify changes protein-RNA interaction landscape...
Adaptive immune responses may be vital in the overall efficacy of oncolytic viruses human malignancies. However, to adenoviruses are poorly understood because these lack activity murine cells, which precludes evaluation immunocompetent cancer models. We have evaluated adenovirus cells. show that a panel carcinoma including CMT64, MOVCAR7, and MOSEC/ID8, can readily infected with adenovirus. These cells also support viral gene transcription, messenger RNA (mRNA) processing, genome...
Next-generation sequencing does not yield fully unbiased estimates for read abundance, which may impact on the conclusions that can be drawn from data. The ligation step in RNA library generation is a known source of bias, motivating developments enzyme technology and construction protocols. We present first comparison standard duplex adaptor protocol supplied by Life Technologies use Ion Torrent PGM with an alternate single approach involving CircLigase (CircLig protocol). A correlation...
Significance Oxidative stress is a critical contributor to aging-associated diseases, including neurodegeneration, cancer, and cardiovascular disease. Here, we demonstrate that the p53 family transcription factor TAp73 contributes oxidative response by participating in control of protein synthesis. Regulation mRNA translation ensures prompt efficient method overcome stress, depletion results aberrant ribosomal biogenesis impaired In particular, important for maintaining active mitochondrial...
Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in cap-dependent machinery. Its role to recruit mRNA ribosome through recognition of 5′-terminal cap structure (m7GpppN, where G guanosine, N any nucleotide). eIF4E implicated cell transformation, tumourigenesis, and angiogenesis by facilitating oncogenic mRNAs; it thus regarded an attractive anticancer drug target. We have used two approaches design cap-binding inhibitors modifying N7-substituent m7GMP...
This paper reports the characterisation of a bacteriocin-like inhibitory substance (BLIS), zoocin A, produced by Streptococcus zooepidemicus strain 4881 that exhibits activity against strains S. mutans, sobrinus and cricetus . A study 98 bacterial using deferred antagonism procedure showed mutans were relatively more sensitive than salivarius sanguis Zoocin was purified from supernate fluid chemically defined medium cultures 4881. Purified (a protein estimated MW 30 000) retained biological...
RNA polymerase III (Pol-III) transcribes tRNAs and other small RNAs essential for protein synthesis cell growth. Pol-III is deregulated during carcinogenesis; however, its role in vivo has not been studied. To address this issue, we manipulated levels of Brf1, a transcription factor that recruitment holoenzyme at tRNA genes vivo. Knockout Brf1 led to embryonic lethality blastocyst stage. In contrast, heterozygous mice were viable, fertile normal size. Conditional deletion gastrointestinal...
This paper reports the characterisation of a bacteriocin-like inhibitory substance (BLIS), zoocin A, produced by Streptococcus zooepidemicus strain 4881 that exhibits activity against strains S. mutans, sobrinus and cricetus. A study 98 bacterial using deferred antagonism procedure showed mutans were relatively more sensitive than salivarius sanguis. Zoocin was purified from supernate fluid chemically defined medium cultures 4881. Purified (a protein estimated MW 30 000) retained biological...
Vulnerability to crisis in newly arrived refugee youth is common as they try come terms with past traumatic experiences and acculturate the new country which have settled. This study examined effects of a short-term music therapy program on changes Behaviour Symptom Index (BSI, Reynolds Kamphus, 1998) 31 youths attending an English language reception centre Brisbane. A cross-over design two five-week intervention periods was employed group sessions conducted one-two times per week. Results...
Abstract The requirement for next generation anti-malarials to be both curative and transmission blockers necessitate the identification of molecular pathways essential viability asexual sexual parasite life stages. Here we identify a selective inhibitor Plasmodium falciparum protein kinase Pf CLK3 which use in combination with chemogenetics, whole genome sequencing transcriptomics validate as druggable target acting at multiple Consistent proposed role regulator RNA splicing, inhibition...
This work was funded by the Medical Research Council. Full open access supported Velux Foundation, University of Zurich, and EPFL School Life Sciences.
Translational regulation plays a central role in the global gene expression of cell, and detection such has allowed deciphering critical biological mechanisms. Genome-wide studies translation (translatome) performed on microarrays represent substantial proportion studies, alongside with recent advances deep-sequencing methods. However, there been lack development specific processing methodologies that deal distinct nature translatome array data. In this study, we confirm polysome profiling...
Abstract We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently malignant pleural mesothelioma (MPM). Here we show, MTAP deletion is negatively prognostic MPM. In vitro, off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced...
Abstract Purpose: Todemonstrate the diagnostic performance of rapid SARS-CoV-2 RT-LAMP assays, comparing genomic versus sub-genomic sequence target with subsequent application in an asymptomatic screening population. Methods: sensitivity (DSe) and specificity (DSp) was determined using 114 RT-PCR clinically positive 88 negative swab samples processed through service within University Hospitals Leicester NHS Trust. A swab-based programme subsequently made available to all staff students at...
The High Intensity Arc Lamr Efficiency of Carbon Pro.jection