PROJECT SUMMARY The AAV BRAIN Safe and Effective Neuromodulator and Sensor Utilization across Species (SENSUS, led by Caltech) of the NIH BRAIN Initiative Armamentarium Project will develop, validate, and disseminate integrated (capsid and genome) engineered adeno-associated virus (AAV) tools to monitor and manipulate molecularly defined neuronal cell types across vertebrate species. To broaden access to these reagents within the neuroscientific community, we propose a close partnership between the AAV BRAIN SENSUS and California State Polytechnic University, Pomona (CPP), which will host a new Armamentarium Vector Core (ArmVC). This collaboration will also increase access to the research community itself for underrepresented minorities (URM) and minority-serving institutions (MSI), as CPP is a designated Hispanic-Serving Institution that also serves large populations of Pell-eligible, first-generation, and African American students. This partnership will foster close interfacing between experts in AAV engineering for neuroscience (PI Gradinaru), AAV production innovations and dissemination (PI Miles), and URM undergraduate research and mentoring (Co-I Steele) to build the physical and human infrastructure for AAV production, validation, and dissemination at CPP while comprehensively integrating MSI undergraduates. Caltech’s CLOVER Center (directed by PI Miles) will utilize their experience in running a successful AAV dissemination center to work with Co-I Steele and Damien Wolfe, M.S., a CPP and Steele lab alum and CLOVER technician who will work at ArmVC, to establish robust AAV production and dissemination capabilities in the ArmVC at CPP (Aim 1). CLOVER and ArmVC will cooperatively run a new AAV BRAIN SENSUS Program for Inclusive Research Experience (ASPIRE) wherein CPP undergraduate students chosen as ASPIRE Scientists will produce validated AAV for dissemination to the neuroscience community as part of the new ArmVC (Aim 2) and work in Co-I Steele’s lab to independently validate, using immunohistochemistry, the novel AAV identified via high-throughput methods in PI Gradinaru’s lab (Aim 3). ASPIRE Scientists will benefit from activities including workshops, poster presentations, research seminars, and career-focused mentoring meetings with PI Gradinaru at CPP and Caltech. Yearly training (and re-training of returning staff and undergraduates) in AAV production by CLOVER staff will ensure that methodological advances in AAV production, purification, and characterization developed or adopted by the CLOVER center are quickly transferred between sites. ArmVC offerings will be publicized and disseminated through a stand-alone website while also being integrated into AAV BRAIN SENSUS electronic resources for seamless reagent cataloguing and feedback. With strong quality control and quality assurance processes in place and overseen by CLOVER, the ArmVC at CPP will broaden access to modern neuroscientific tools and help bridge the gap in URM career progression in research science.

PROJECT NARRATIVE This project will pair the NIH-funded AAV BRAIN Safe and Effective Neuromodulator and Sensor Utilization across Species (SENSUS, led by Caltech) with California State Polytechnic University, Pomona (CPP) to build a new Armamentarium Vector Core (ArmVC), broadening the Armamentarium project’s ability to validate and disseminate the next generation of modern gene delivery tools to understand and, eventually, treat the brain. In addition, ArmVC will help to build a new, more diverse brain gene therapy workforce through the AAV BRAIN SENSUS Program for Integrated Research Experiences (ASPIRE). As ASPIRE Scientists, undergraduates from CPP—a designated Hispanic-Serving Institution that also serves a large number of Pell-eligible, first-generation, and African American students—will receive extensive training and mentoring both at Caltech and CPP while broadening novel AAV validation, production, and dissemination through ArmVC.