Bross, M. | Search bioRxiv

bioRxiv2023

Too many big promises: What is holding back cyanobacterial research and applications?

Climate change as a global crisis demands a shift from a fossil fuel-based economy to-wards sustainable solutions. Cyanobacteria are promising organisms for the truly sustainable, carbon-neutral production of various chemicals. However, so far, proof of concepts for large-scale cyanobacterial productions that produce industrial-relevant amounts of desired products are lacking. To systematically address this topic, a comprehensive overview that identifies current obstacles and solutions is missing. We conducted a quantitative survey among researchers in the cyanobacterial community. This work investigates individual experiences and challenges in the field of cyanobacteria, as well as information about specific protocols. Additionally, qualitative interviews with academic experts were conducted. Their answers were compared, and highlights were summarised. In this work, we provide for the first time a comprehensive overview of current trends and challenges as perceived by researchers in the field of cyanobacteria. Based on the results of the survey and interviews, we formulate a set of recommendations on how to improve the working conditions within the cyanobacteria research community.

microbiology↗

bioRxiv2023

Host genetic background regulates the capacity for anti-tumor antibody-dependent phagocytosis

BackgroundAntitumor antibody, or targeted immunotherapy, has revolutionized cancer treatment and markedly improved patient outcomes. A prime example is the monoclonal antibody (mAb) trastuzumab, which targets human epidermal growth factor receptor 2 (HER2). However, like many targeted immunotherapies, only a subset of patients benefit from trastuzumab long-term. In addition to tumor-intrinsic factors, we hypothesize that host genetics may influence subsequent immune activation. MethodsTo model the human population, we produced F1 crosses of genetically heterogeneous Diversity Outbred (DO) mice with BALB/c mice (DOCF1). Distinct DOCF1 mice were orthotopically implanted with the BALB/c-syngeneic TUBO mammary tumor line, which expresses the HER2 ortholog rat neu. Treatment with anti-neu mAb clone 7.16.4 began once tumors reached [~]200 mm3. Genetic linkage and quantitative trait locus (QTL) effects analyses in R/qtl2 identified loci associated with tumor growth rates. Locus validation was performed with BALB/c F1 crosses with recombinant-inbred Collaborative Cross (CC) strains selected for therapy-associated driver genetics (CCxCF1). The respective roles of natural killer (NK) cells and macrophages were investigated by selective depletion in vivo. Ex vivo macrophage antibody-dependent phagocytosis (ADCP) assays were evaluated by confocal microscopy using 7.16.4-opsonized E2Crimson-expressing TUBO tumor cells. ResultsWe observed a divergent response to anti-tumor antibody therapy in DOCF1 mice. Genetic linkage analysis detected a locus on chromosome 10 that correlates to a robust response to therapy, which was validated in CCxCF1 models. Single-cell RNA sequencing of tumors from responder and non-responder models identified key differences in tumor immune infiltrate composition, particularly within macrophage (M{varphi}) subsets. This is further supported by ex vivo analysis showing M{varphi} ADCP capacity correlates to in vivo treatment outcomes in both DOCF1 and CCxCF1 models. ConclusionsHost genetics play a key regulatory role in targeted immunotherapy outcomes, and putative causal genes are identified in murine chromosome 10 which may govern M{varphi} function during ADCP.

cancer biology↗