I’m pleased to announced that two pieces of work I’ve co-authored are now live on bioRxiv:

In the first, “Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood“, from Jacqueline Siu, we look at human B cell differentiation and dissemination using multiple different technologies, and uncover two distinct subsets of marginal zone B cells. We explore the differences between these subsets in terms of cell surface and transcriptomic profiles, clonal dissemination, hypermutation frequency, and micro-anatomical distribution in healthy spleen, mesenteric lymph node and appendix, and compare them in the blood of healthy patients and those with lupus.

In the second, “A SIMPLI (Single-cell Identification from MultiPLexed Images) approach for spatially resolved tissue phenotyping at single-cell resolution”, from the Ciccarelli Lab, presents a novel technology-agnostic software that unifies all steps of multiplexed imaging data analysis. This new software is shown in action by studying the human colon mucosa for IgA and the human appendix for T follicular helper cells.

Our latest paper has now been published in the Journal of Experimental Medicine: link here. See also this piece from David Nemazee exploring the context of our work.

Abstract:

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgM^hi and IgM^lo developmental trajectories. IgM^hi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgM^lo branch and are selectively recruited into gut-associated lymphoid tissue. IgM^hi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgM^hi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgM^hi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgM^hi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health.

Our latest editorial piece from the Infection and Global Health Research Division at the University of St Andrews on the need for mechanistic modelling of within-host tuberculosis dynamics, entitled “How mechanistic in silico modelling can improve our understanding of TB disease and treatment”, is now live in the International Journal of Tuberculosis and Lung disease: link here.

Abstract:

TB is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent. Decreasing the length of time for TB treatment is an important step towards the goal of reducing mortality. Mechanistic in silico modelling can provide us with the tools to explore gaps in our knowledge, with the opportunity to model the complicated within-host dynamics of the infection, and simulate new treatment strategies. Significant insight has been gained using this form of modelling when applied to other diseases – much can be learned in infection research from these advances.

Our latest work from the Spencer Lab and collaborators is now online at bioRxiv! In it, we look at B cell development and show how these cells follow distinct IgM high and low trajectories, and the implications this has for lupus. You can read our work here.

Our latest paper (the final one from my PhD work) is now published. In “Modelling the effects of environmental heterogeneity within the lung on the tuberculosis life-cycle“, we created a model that incorporates the environmental heterogeneity of conditions such as blood perfusion and oxygen tension within the lung to investigate the effects they had on the whole tuberculosis life-cycle, demonstrating how different parameters affect different stages of infection and show how the environmental differentials can drive post-primary disease (where most transmission occurs) to the oxygen-rich apices of the lung.