E11 Bio - Scientist/Senior Scientist, Molecular Engineering & Sample Optimization

Job description

[E11 Bio](http://e11.bio/) is on a mission to advance connectomics towards whole brain scale for humans and other mammals. We are a collaborative and interdisciplinary team of scientists and engineers engaged in a neuroscience moonshot project to develop a radical technology platform for scalable mammalian brain mapping. E11 Bio is a non-profit Convergent Research focused research organization located in Alameda, California, pursuing blue-skies neuroscience research yet operating like a nimble, tight-knit start-up. Read our [technology roadmap](https://e11.bio/news/roadmap). E11 Bio is seeking a mission-aligned experimental scientist, equally at home at the bench, the microscope, and in quantitative data analysis, who brings an engineering approach to the full pipeline, from sample preparation through molecular readout tools. This role owns both optimizing the physical preparation of the tissue and engineering the reagent panels across two target types: comprehensive synapse identification and barcode epitopes. Reporting to the Barcoding Lead, you will define what high-quality tissue means quantitatively and will drive the improvement of high quality morphology and protein readout by working closely with molecular biology, imaging, and computational teams to support whole-brain connectomics. ### Responsibilities - Develop and deploy an assay to systematically evaluate and improve the fixation quality and preservation of brain tissue - Establish and integrate quantitative metrics of molecular readout e.g. protein retention, antigenicity, and labeling quality across tissue preparation conditions - Work closely with in vivo research technicians to design experiments, evaluate results, and optimize SOPs - Drive the development of data-analysis pipelines to routinely generate key performance indicators of sample tissue quality - Generate an in-house pipeline for binder design/discovery, validation, and optimization of epitope-binder pairs in hydrogels to improve the readout of epitope barcode bits and relevant native synaptic proteins - Develop novel highly multiplexed protein readout strategies for protein barcodes and molecular annotation of synapses and cell types ### Outcomes ### **In the first 6 Months** - Defined key indicators for perfusion quality and deploy an assay to routinely capture these. - Incorporated protein retention, antigenicity, and specificity as per-stage metrics across the sample generation pipeline. - Deployed early perfusion or fixed tissue readout metrics that predict the final expanded tissue quality, including both overall preservation and specific markers of cellular health - Recorded a measurable > 20%improvement in expanded ultrastructural image contrast compared to current baseline perfusion & gelation protocol - First new epitope-binder designs in production - Developed assay for binder compatibility in expanded tissue, and validated this assay against existing pairs - Identified and validated a cocktail of binders for identifying most synapses via e.g. synaptic vesicle binding ### ### **In 12 Months:** - Evaluated the first set of designed epitope-binder pairs and synaptic protein-binder pairs and qualified in expanded tissue, 5+ binders exceeding commercial SOTA performance. - With collaborators, improved the multiplexed readout strategy to allow for routine incorporation into the imaging pipeline and a demonstrated increase in key barcode metrics (e.g. imaging speed or entropy increases) - Identified and validated multiple cocktails of binders for stratifying excitatory and inhibitory synapses ###