Biology subjects

Elliot, A.

Publications and source records attributed to Elliot, A..

4 recordsLinked to original sources

bioRxiv2026

Single cell analysis reveals molecular traits of pediatric lymphoma resistant subclones

The cause of refractory/relapse (R/R) in pediatric lymphoma is unclear. We hypothesized that a stem-like, chemoresistance lymphoma subclone may contribute to R/R. Combining single cell RNA sequencing (scRNA-seq) and immune receptor sequencing (scVDJ-seq) on freshly acquired pediatric non-Hodgkin lymphoma (pNHL n=10), Hodgkin lymphoma (pHL n=5), and 10 reactive lymph nodes from adults or children (a/pReLy), we discovered pediatric-specific progenitor-like lymphocytes, whose cellular program was enriched in pNHL subclones emerging late during clonal evolution, accompanied by loss of immune receptor expression. R-CHOP target gene expression indicated that these subclones may escape first-line treatment, and suggested MSI2, an RNA binding protein, as a potential target. In pHL, the progenitor-like program was found in the tumor microenvironment (TME) but not Hodgkin cells which, during relapse, were myeloid-like and accompanied by CD74highCCL5+ CD8 T cells. In summary, we discovered R/R associated lymphoma subclones in pediatric lymphoma and potential ways to eradicate them. Key messagesO_LIProgenitor-like lymphocytes are uniquely found in pediatric reactive lymph nodes, but not in adults. C_LIO_LIResistant subclones from pNHL acquire progenitor-like program and share MSI2 expression. C_LIO_LIRelapsed Hodgkin cells are monocyte-like and recruit CD74highCCL5+ CD8 T cells. C_LI

cancer biology↗

bioRxiv2025

Microtubule curling as an efficient readout to uncover fundamental concepts of axonal cell biology

Nerve fibres (aka axons) are the slender, up-to-meter-long processes of nerve cells that wire nervous systems. These delicate structures must survive for an organisms lifetime, making them prime lesion sites in neurodegeneration. Their long-term maintenance requires the homeostasis of complex local cell biology upheld by motor protein-driven transport along microtubule bundles that run uninterrupted along axons. To gain an understanding of axonal homeostasis, we report and discuss here the functional loss of 105 genes from a wide range of cell biological processes using a standardised Drosophila primary neuron system. [~]40% of these gene deficiencies caused microtubule bundle disturbances referred to as microtubule-curling, which we use as an indicator of axonal atrophy. Our live imaging showed that microtubule-curling initiates in areas where axons widen, such as areas close to the soma, branch points or growth cones. In wild-type neurons, any initiated curling was contained, but it persisted as growing footprints in mutant curl-promoting conditions. Closer analyses of 20 curl-promoting conditions suggested a general classification into two groups: mutations affecting axonal physiology cause ROS-mediated microtubule-curling, whereas mutations causing motor hyperactivation or affecting microtubule-regulating proteins cause structurally induced ROS-independent curling. As will be discussed, our data provide consistent support for the previously proposed dependency cycle of local axon homeostasis model which can explain the long-standing conundrum that genes from a wide range of cell biological processes often have mutational links to the same class of inherited neurodegenerative disease.

cell biology↗

bioRxiv2024

Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic Schistosoma mansoni

Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles. One Sentence SummaryPopulation genomics and functional genetics of praziquantel resistance in Schistosoma mansoni

genomics↗

bioRxiv2018

Temperate grass allergy season defined by spatio-temporal shifts in airborne pollen communities

Grass pollen is the worlds most harmful outdoor aeroallergen and sensitivity varies between species. Different species of grass flower at different times, but it is not known how airborne communities of grass pollen change in time and space. Persistence and high mobility of grass pollen could result in increasingly diverse seasonal pollen communities. Conversely, if grass pollen does not persist for an extended time in the air, shifting pollen communities would be predicted throughout the summer months. Here, using targeted high throughput sequencing, we tracked the seasonal progression of airborne Poaceae pollen biodiversity across Britain, throughout the grass allergy season. All grass genera displayed discrete, temporally restricted peaks of pollen incidence which varied with latitude, revealing that the taxonomic composition of grass pollen exposure changes substantially across the allergy season. By developing more refined aeroallergen profiling, we predict that our findings will facilitate the exploration of links between taxon-specific exposure of harmful grass pollen and disease, with concomitant socio-economic benefits.

ecology↗