Dorris, E. R. | Search bioRxiv

bioRxiv2019

Subcellular localization of the immunoregulatory protein MACIR by TNPO1 is mediated by a C terminal PY motif

Expression of the macrophage immunometabolism regulator gene (MACIR) is associated with severity of autoimmune disease pathology and the regulation of macrophage biology through unknown mechanisms. The 206 amino acid protein lacks homology to any characterized protein sequence and is a disordered protein according to structure prediction algorithms. Here we identify specific interactions of MACIR using a fragment complementation-based affinity pull down of cellular proteins prepared with a membrane solubilization buffer. Quantitative mass spectrometry showed enrichment of nuclear and mitochondrial proteins and of 63 significant interacting proteins, binding to the nuclear transport receptor TNPO1 and trafficking proteins UNC119 homolog A and B were validated by immunoprecipitation. Analysis of mutations in two candidate recognition motifs in the MACIR amino acid sequence confirmed TNPO1 binds via a PY-NLS motif (aa98-117). Characterizing nuclear MACIR activity in macrophage and fibroblasts is a priority with respect to developing strategies for treatment of autoimmune disease.

biochemistry↗

bioRxiv2019

From intent to implementation: Factors affecting public involvement in life science research

Public involvement is key to closing the gap between research production and research use, and the only way to achieving ultimate transparency in science. The majority of life science research is not public-facing, but is funded by the public and impacts the community. We undertook a survey of researchers within the life sciences to better understand their views and perceived challenges to involving the public in their research. We had a valid response cohort of n=110 researchers, of whom 90% were primarily laboratory based. Using a mixed methods approach, we demonstrate that a top-down approach is key to motivate progression of life scientists from feeling positive towards public involvement to actually engaging in it. Researchers who viewed public involvement as beneficial to their research were more likely to have direct experience of doing it. We demonstrate that the systemic flaws in the way life sciences research enterprise is organised, including the promotion system, hypercompetition, and time pressures are major barriers to involving the public in the scientific process. Scientists are also apprehensive of being involuntarily involved in the current politicized climate, misinformation and publicity hype surrounding science nowadays makes them hesitant to share their early and in-progress research. The time required to deliberate study design and relevance, plan and build relationships for sustained involvement, provide and undertake training, and improve communication in the current research environment is often considered nonpragmatic, particularly for early career researchers. In conclusion, a top-down approach involving institutional incentives and infrastructure appears most effective at transitioning researchers from feeling positive towards public involvement to actually implementing it.

scientific communication and education↗