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Biology subjects

Martin, T. G.

Publications and source records attributed to Martin, T. G..

2 recordsLinked to original sources

Prioritizing conservation actions for Pacific salmon in Canada

O_LICurrent investment in conservation is insufficient to adequately protect and recover all ecosystems and species. The challenge of allocating limited funds is acute for Pacific salmon (Oncorhynchus spp.) in Canada, which lack a strategic approach to ensure that resources are spent on actions that would cost-effectively recover diminished populations. C_LIO_LIWe applied the Priority Threat Management framework to prioritize strategies that are most likely to maximize the number of thriving Pacific salmon populations on the Central Coast of British Columbia, Canada. These included 79 genetically, ecologically and spatially distinct population groups called Conservation Units (CUs) for five salmon species. This region has high salmon biodiversity and spans the territories of four First Nations: the Heiltsuk, Nuxalk, Kitasoo/Xaixais and Wuikinuxv. C_LIO_LIUsing structured expert elicitation of Indigenous and other experts, we quantified the estimated benefits, costs and feasibility of implementing 10 strategies. Under a business-as-usual scenario (i.e., no additional investments in salmon conservation or management), experts predicted that only one in four CUs would have >50% chance of achieving a thriving status within 20 years. Limiting future industrial development, which was predicted to safeguard CUs from future declines, was identified as the most cost-effective strategy. Investment in three strategies: 1) removal of artificial barriers to fish migration, 2) watershed protection, and 3) stream restoration - at 11.3M CAD per year - was predicted to result in nearly half (34 of 79) of the CUs having a >60% chance of meeting the conservation objective. C_LIO_LIIf all conservation strategies were implemented, experts estimated a >50% probability of achieving a thriving status for 78 of 79 CUs, at an annual cost of 17.3M CAD. However, even with the implementation of all strategies, most sockeye salmon CUs were unlikely to achieve higher probability targets of reaching the objective. C_LIO_LIPolicy implications: We illustrate how Priority Threat Management can incorporate the perspectives and expertise of Indigenous peoples and other experts to evaluate and prioritize conservation strategies based on their cost, benefit and feasibility. Timely investment in the strategies outlined in this assessment could help safeguard and recover Pacific salmon in this region of Canada. C_LI

ecology

CRISPR-based screens uncover determinants of immunotherapy response and potential combination therapy strategies

Cancer cells commonly develop resistance to immunotherapy by loss of antigen expression. Combinatorial treatments that increase levels of the target antigen on the surface of cancer cells have the potential to restore efficacy to immunotherapy. Here, we use our CRISPR interference and CRISPR activation-based functional genomics platform to systematically identify pathways controlling cell-surface expression of the multiple myeloma immunotherapy antigen - B cell maturation antigen, BCMA. We discovered that pharmacological inhibition of HDAC7 and the Sec61 complex increased cell-surface BCMA, including in primary patient cells. Importantly, pharmacological Sec61 inhibition enhanced the anti-myeloma efficacy of a BCMA-targeted antibody-drug conjugate. A CRISPR interference CAR-T coculture screen enabled us to identify both antigen-dependent and -independent mechanisms controlling response of myeloma cells to BCMA-targeted CAR-T cells. Thus, our study demonstrates the potential of CRISPR screens to uncover mechanisms controlling response of cancer cells to immunotherapy and to suggest potential combination therapies. Key PointsO_LIUsing CRISPR screens, we systematically identify mechanisms increasing expression of the immunotherapy target BCMA and ADC efficacy. C_LIO_LIWe also identify antigen-independent mechanisms regulating response of cancer cells to BCMA-CAR-T cells. C_LI

cancer biology