Biology subjects

So, T.

Publications and source records attributed to So, T..

3 recordsLinked to original sources

bioRxiv2023

Fate-mapping lymphocyte clones and their progenies from induced antigen-signals identifies temporospatial behaviours of T cells mediating tolerance

Tissue homeostasis is maintained by the behaviours of lymphocyte clones responding to antigenic triggers in the face of pathogen, environmental, and developmental challenges. Current methodologies for tracking the behaviour of specific lymphocytes identify clones of a defined antigen-receptor--antigen binding affinity. However, lymphocytes can receive antigenic signals from undefined or endogenous antigens, and the strength of each signal, even for the same lymphocyte, varies with accessory signalling, across tissues and across time. We present a novel fate-mapping mouse, that, by tracking lymphocyte clones and their progenies from induced antigen signals, overcomes these hurdles and provides novel insights into the maintenance of tissue homeostasis. We demonstrate the systems use by investigating the maintenance of localised T cell tolerance in tumour immunity. In a murine tumour model, our system reveals how Tregs differentiate to a reversible, tolerance inducing state within the tumour, and recirculate, while CD8+ T cells failing to recirculate, differentiate to an increasingly exhausted, tolerant state in the tumour. These contrasting T cell behaviours provide means by which immunity can tolerate a particular anatomical niche while maintaining systemic clonal protection. Our system can thus explore lymphocyte behaviours that cannot be tracked by previous methods and will therefore provide novel insights into the fundamental mechanisms underlying immunitys role in tissue homeostasis.

immunology↗

bioRxiv2023

Range-wide differential adaptation and genomic vulnerability in critically endangered Asian rosewoods

In the billion-dollar global illegal wildlife trade, rosewoods have been the worlds most trafficked wild product since 20051. Dalbergia cochinchinensis and D. oliveri are the most sought-after rosewoods in the Greater Mekong Subregion2. They are exposed to significant genetic risks and the lack of knowledge on their adaptability limits the effectiveness of conservation efforts. Here we present genome assemblies and range-wide genomic scans of adaptive variation, together with predictions of genomic vulnerability to climate change. Adaptive genomic variation was differentially associated with temperature and precipitation-related variables between the species, although their natural ranges overlap. The findings are consistent with differences in pioneering ability and in drought tolerance3. We predict their genomic offsets will increase over time and with increasing carbon emission pathway but at a faster pace in D. cochinchinensis than in D. oliveri. These results and the distinct gene-environment association in the eastern coastal edge suggest species-specific conservation actions: germplasm representation across the range in D. cochinchinensis and focused on vulnerability hotspots in D. oliveri. We translated our genomic models into a seed source matching application, seedeR, to rapidly inform restoration efforts. Our ecological genomic research uncovering contrasting selection forces acting in sympatric rosewoods is of relevance to conserving tropical trees globally and combating risks from climate change. Significant statementIn the billion-dollar global illegal wildlife trade, rosewoods have been the worlds most trafficked wild product since 2005, with Dalbergia cochinchinensis and D. oliveri being the most sought-after and endangered species in Southeast Asia. Emerging efforts for their restoration have lacked a suitable evidence base on adaptability and adaptive potential. We integrated range-wide genomic data and climate models to detect the differential adaptation between D. cochinchinensis and D. oliveri in relevance to temperature- and precipitation-related variables and projected their vulnerability until 2100. We highlighted the stronger local adaptation in the coastal edge of the species ranges suggesting conservation priority. We developed genomic resources including chromosome-level genome assemblies and a web-based application seedeR for genomic model-enabled assisted migration and restoration.

genomics↗

bioRxiv2023

Microfluidics-enabled fluorescence-activated cell sorting of single pathogen-specific antibody secreting cells for the rapid discovery of monoclonal antibodies

Monoclonal antibodies are increasingly used to prevent and treat viral infections, playing a pivotal role in pandemic response efforts. Antibody secreting cells (ASCs, plasma cells and plasmablasts) are an excellent source of high-affinity antibodies with therapeutic potential. Current methodologies to study antigen-specific ASCs either have low throughput, require expensive and labour-intensive screening or are technically demanding and therefore not accessible to the wider research community. Here, we present a straightforward technology for the rapid discovery of monoclonal antibodies from ASCs: we combine microfluidic encapsulation of single cells into an antibody capture hydrogel with antigen bait sorting by conventional flow cytometry. With our technology, we screened millions of mouse and human ASCs and obtained anti-SARS-CoV-2 monoclonal antibodies with high affinity (pM) and neutralising capacity (<100 ng/mL) in two weeks with a high hit rate (>85%). By facilitating access into the underexplored ASC compartment, we enable fast and efficient antibody discovery as well as immunological studies into the generation of protective antibodies.

immunology↗