ORCID Profile
0000-0001-7151-3207
Current Organisation
Cardiff University
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Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0AN02381G
Abstract: Quantitative hyperspectral coherent Raman scattering microscopy merges imaging with spectroscopy and utilises quantitative data analysis algorithms to extract chemical components, spectrally and spatially-resolved, with sub-cellular resolution.
Publisher: The American Association of Immunologists
Date: 05-2017
Publisher: Cold Spring Harbor Laboratory
Date: 08-05-2019
DOI: 10.1101/631754
Abstract: The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus . We recently posited that genetic ersity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflect differences in subspecies origin. To investigate this hypothesis, we conducted high-throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ), and ersity (IGHD) genes in four inbred wild-derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ, and PWD/PhJ), and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild-derived strains, including 247 not curated in the International Immunogenetics Information System. In contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. In contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of ersity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand inter-strain variation in models of antibody-mediated disease.
Publisher: Cold Spring Harbor Laboratory
Date: 29-12-2017
DOI: 10.1101/240747
Abstract: Female Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, has been slowed by the lack of a high-quality genome assembly. Here we combine erse genome technologies to produce AaegL5, a dramatically improved and annotated assembly, and demonstrate how it accelerates mosquito science and control. We anchored the physical and cytogenetic maps, resolved the size and composition of the elusive sex-determining “M locus”, significantly increased the known members of the glutathione-S-transferase genes important for insecticide resistance, and doubled the number of chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites. Using high-resolution QTL and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. We predict that AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly arboviral vector.
Publisher: Springer Science and Business Media LLC
Date: 21-07-2023
DOI: 10.1038/S41467-023-40070-X
Abstract: Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes in iduals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 17-07-2020
Abstract: Deaths caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in New York City (NYC) during the spring of 2020 have vastly exceeded those reported in China and many other countries. What were the early events that led to such a severe outbreak? Gonzalez-Reiche et al. s led some of the early patients seeking assistance in February and March of 2020 at the Mount Sinai Health System. Phylogenetic analysis of virus sequences in these people, who were drawn from across NYC, showed that the virus had been independently introduced many times from Europe and elsewhere in the United States. Subsequent clusters of community transmission occurred. The focus of infection in NYC is a marker of the role this city plays as a two-way hub for human movement. Science this issue p. 297
Publisher: Wiley
Date: 23-02-2011
DOI: 10.1002/GLIA.21143
Abstract: Malignant glioma is among of the most devastating, and least curable, types of cancer. Since the re‐emergence of the cancer stem cell hypothesis, much progress has been made towards elucidating the cellular origin of these tumors. The hypothesis that tumors are hierarchically organized, with a cancer stem cell at the top that shares defining features with somatic stem cells and provides therapeutic refractoriness properties, has put adult stem cells into the limelight as prime suspect for malignant glioma. Much confusion still exists, though, as to the particular cell type and processes that lead to oncogenic transformation. In this review, we will discuss recent developments and novel hypotheses regarding the origin of malignant gliomas, especially glioblastoma. In particular, we argue that glioblastoma is the result of different pathways originating in multiple sources that all ultimately converge in the same disease. Further attention is devoted to potential scenarios leading to transformation of different stem rogenitor cell types of the brain, and the probability and relevance of these scenarios for malignant tumorigenesis. © 2011 Wiley‐Liss, Inc.
Publisher: Wiley
Date: 06-10-2019
DOI: 10.1111/IMCB.12288
Abstract: The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic ersity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflects differences in subspecies origin. To investigate this hypothesis, we conducted high-throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ) and ersity (IGHD) genes in four inbred wild-derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ and PWD/PhJ) and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild-derived strains, including 247 not curated in the international ImMunoGeneTics information system. By contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. By contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of ersity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand interstrain variation in models of antibody-mediated disease.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Melissa Smith.