Megan Palmer: we must build a world where everyone, everywhere, can build with biology

Advances in synthetic biology are enabling the engineering of biological components to build applications in a wide array of fields, from medicine to manufacturing and beyond. The benefits of synthetic biology to solving global challenges are immense, but there are concerns about new forms of misuse it might enable. To safeguard our future, the executive director of bio policy and leadership initiatives at Stanford University, Megan Palmer, says we need to enable everyone to build with biology and to bake biosecurity into the pursuit of peaceful purposes. Dr Palmer sat down for a brief Q&A with LSE Business Review’s managing editor, Helena Vieira, during the World Economic Forum’s Great Narrative meeting in Dubai

Signaling thresholds govern heterogeneity in IL-7-receptor-mediated responses of naïve CD8+ T cells

Variable sensitivity to T-cell-receptor (TCR)- and IL-7-receptor (IL-7R)-mediated homeostatic signals among naïve T cells has thus far been largely attributed to differences in TCR specificity. We show here that even when withdrawn from self-peptide-induced TCR stimulation, CD8+ T cells exhibit heterogeneous responses to interleukin-7 (IL-7) that are mechanistically associated with IL-7R expression differences that correlate with relative CD5 expression. Whereas CD5hi and CD5lo T cells survive equivalently in the presence of saturating IL-7 levels in vitro, CD5hi T cells proliferate more robustly. Conversely, CD5lo T cells exhibit prolonged survival when withdrawn from homeostatic stimuli. Through quantitative experimental analysis of signaling downstream of IL-7R, we find that the enhanced IL-7 responsiveness of CD5hi T cells is directly related to their greater surface IL-7R expression. Further, we identify a quantitative threshold in IL-7R-mediated signaling capacity required for proliferation that lies well above an analogous threshold requirement for survival. These distinct thresholds allow subtle differences in IL-7R expression between CD5lo and CD5hi T cells to give rise to significant variations in their respective IL-7-induced proliferation, without altering survival. Heterogeneous IL-7 responsiveness is observed similarly in vivo, with CD5hi naïve T cells proliferating preferentially in lymphopenic mice or lymphoreplete mice administered with exogenous IL-7. However, IL-7 in lymphoreplete mice appears to be maintained at an effective level for preserving homeostasis, such that neither CD5hi IL-7Rhi nor CD5lo IL-7Rlo T cells proliferate or survive preferentially. Our findings indicate that IL-7R-mediated signaling not only maintains the size but also impacts the diversity of the naïve T-cell repertoire

Rapid proliferation of pandemic research: implications for dual-use risks

The COVID-19 pandemic has demonstrated the world’s vulnerability to biological catastrophe and elicited unprecedented scientific efforts. Some of this work and its derivatives, however, present dual-use risks (i.e., potential harm from misapplication of beneficial research) that have largely gone unaddressed. For instance, gain-of-function studies and reverse genetics protocols may facilitate the engineering of concerning SARS-CoV-2 variants and other pathogens. The risk of accidental or deliberate release of dangerous pathogens may be increased by large-scale collection and characterization of zoonotic viruses undertaken in an effort to understand what enables animal-to-human transmission. These concerns are exacerbated by the rise of preprint publishing that circumvents a late-stage opportunity for dual-use oversight. To prevent the next global health emergency, we must avoid inadvertently increasing the threat of future biological events. This requires a nuanced and proactive approach to dual-use evaluation throughout the research life cycle, including the conception, funding, conduct, and dissemination of research

iGEM: a model system for team science and innovation

Teams are a primary source of innovation in science and technology. Rather than examining the lone genius, scholarly and policy attention has shifted to understanding how team interactions produce new and useful ideas. Yet the organizational roots of innovation remain unclear, in part because of the limitations of current data. This paper introduces the international Genetically Engineered Machine (iGEM) competition, a model system for studying team science and innovation. By combining digital laboratory notebooks with performance data from 2,406 teams over multiple years of participation, we reveal shared dynamical and organizational patterns across teams and identify features associated with team performance and success. This dataset makes visible organizational behavior that is typically hidden, and thus understudied, creating new opportunities for the science of science and innovation.Comment: 78 pages including SI, 7 figures, 18 SI figure

Urinary Levoglucosan as a Biomarker of Wood Smoke Exposure: Observations in a Mouse Model and in Children

BACKGROUND: Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulose-containing materials, is an attractive candidate as a biomarker of wood smoke exposure. OBJECTIVES: In the present study, Balb/c mice and children were assessed for LG in urine to determine its feasibility as a biomarker. METHODS: We performed urinary detection of LG by gas chromatography/mass spectrometry after intranasal instillations of LG or concentrated PM (mice) or biomass exposure (mice or humans). RESULTS: After instillation, we recovered most of the LG within the first 4 hr. Experiments using glucose instillation proved the specificity of our system, and instillation of concentrated PM from wood smoke, ambient air, and diesel exhaust supported a connection between wood smoke and LG. In addition, LG was detected in the urine of mice exposed to wood smoke. Finally, a pilot human study proved our ability to detect LG in urine of children. CONCLUSIONS: These results demonstrate that LG in the lungs is detectable in the urine of both mice and humans and that it is a good candidate as a biomarker of exposure to biomass smoke

GPI spectra of HR 8799 c, d, and e from 1.5 to 2.4μ\mum with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in H & K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same dataset. We also present a K band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H & K spectra, but do not find any conclusive differences between d and e or c and e, likely due to large error bars in the recovered spectrum of e. Compared to M, L, and T-type field brown dwarfs, all three planets are most consistent with mid and late L spectral types. All objects are consistent with low gravity but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets' near-IR flux and discuss how differences between the properties of these planets can be further explored.Comment: Accepted to AJ, 25 pages, 16 Figure

Guiding Ethical Principles in Engineering Biology Research

Engineering biology is being applied toward solving or mitigating some of the greatest challenges facing society. As with many other rapidly advancing technologies, the development of these powerful tools must be considered in the context of ethical uses for personal, societal, and/or environmental advancement. Researchers have a responsibility to consider the diverse outcomes that may result from the knowledge and innovation they contribute to the field. Together, we developed a Statement of Ethics in Engineering Biology Research to guide researchers as they incorporate the consideration of long-term ethical implications of their work into every phase of the research lifecycle. Herein, we present and contextualize this Statement of Ethics and its six guiding principles. Our goal is to facilitate ongoing reflection and collaboration among technical researchers, social scientists, policy makers, and other stakeholders to support best outcomes in engineering biology innovation and development