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Lukhele, S.

Publications and source records attributed to Lukhele, S..

2 recordsLinked to original sources

Enable, Empower, Succeed: Harnessing Open Science for Antimicrobial Resistance Containment

Antimicrobial resistance (AMR) poses a significant threat to global health, particularly in Western sub-Saharan Africa where 27.3 deaths per 100,000 lives are affected, and surveillance and control measures are often limited. Genomics research plays a crucial role in understanding the emergence, spread and containment measures of AMR. However, its implementation in such settings is particularly challenging due to limited human capacity. This manuscript outlines a three-day bioinformatics workshop in Cameroon, highlighting efforts to build human capacity for genomics research to support AMR surveillance using readily accessible and user-friendly web-based tools. The workshop introduced participants to basic next-generation sequencing concepts, data file formats used in bacterial genomics, data sharing procedures and considerations, as well as the use of web-based bioinformatics software to analyse genomic data, including in silico prediction of AMR, phylogenetics analyses, and a quick introduction to Linux(C) command line. We provide a detailed description of the relevant training approaches used, including workshop structure, the selection and planning, and utilization of freely available web-based tools, and the evaluation methods employed. Our approach aimed to overcome limitations such as inadequate infrastructure, limited access to computational resources, and scarcity of expertise. By leveraging the power of freely available web-based tools, we demonstrated how participants can acquire fundamental bioinformatics skills, enhance their understanding of biological data analysis, and contribute to the field, even in an underprivileged environment. Our findings highlight the effectiveness of this training approach in empowering local researchers and bridging the bioinformatics gap in genomics surveillance of AMR in resource-constrained settings. Building human capacity for genomics research globally, and especially in resource-constrained settings, is imperative for ensuring global health and sustainable containment of AMR. Data summaryThe authors confirm that all supporting data, code and protocols have been provided within the article or through supplementary data files. Impact StatementAntimicrobial resistance (AMR) is a major global health threat, especially in Western sub-Saharan Africa, where 27.3 deaths per 100,000 lives occur. Genomics research play an instrumental role for understanding AMRs emergence, spread, and containment measures. However, its implementation in these settings is challenging due to limited human capacity. A three-day bioinformatics workshop in Cameroon aimed to build human capacity for genomics research using web-based tools. Participants were introduced to next-generation sequencing concepts, data file formats, data sharing procedures, and web-based bioinformatics software for analysing genomic data. The workshop aimed to overcome limitations like inadequate infrastructure, computational resources, and expertise scarcity. The findings show the effectiveness of this training approach in empowering local researchers and bridging the bioinformatics gap in genomics surveillance of AMR in resource-constrained settings.

scientific communication and education↗

Molecular, metabolic and functional CD4 T cell paralysis impedes tumor control

CD4 T cells are important effectors of anti-tumor immunity, yet the regulation of CD4 tumor-specific T (TTS) cells during cancer development is still unclear. We demonstrate that CD4 TTS cells are initially primed in the tumor draining lymph node and begin to divide following tumor initiation. Distinct from CD8 TTS cells and previously defined exhaustion programs, CD4 TTS cell proliferation is rapidly frozen in place and differentiation stunted by a functional interplay of T regulatory cells and both intrinsic and extrinsic CTLA4 signaling. Together these mechanisms paralyze CD4 TTS cell differentiation, redirecting metabolic and cytokine production circuits, and reducing CD4 TTS cell accumulation in the tumor. Paralysis is actively maintained throughout cancer progression and CD4 TTS cells rapidly resume proliferation and functional differentiation when both suppressive reactions are alleviated. Strikingly, Treg depletion alone reciprocally induced CD4 TTS cells to themselves become tumor-specific Tregs, whereas CTLA4 blockade alone failed to promote T helper differentiation. Overcoming their paralysis established long-term tumor control, demonstrating a novel immune evasion mechanism that specifically cripples CD4 TTS cells to favor tumor progression.

cancer biology↗