PROJECT SUMMARY The proposed “Blood-Brain Barrier” (BBB) meeting to be held at Cold Spring Harbor Laboratory (CSHL) from April 3rd - 6th 2019, will assemble leaders in the fields of BBB, blood-retina barrier (BRB) or blood-cerebrospinal fluid (CSF) barrier to discuss recent discoveries and future directions. This application seeks support for the sixth meeting of a biennial series of meetings held at CSHL on the topic of the brain barriers. This meeting has emerged as a premiere scientific conference focused on the molecular and cellular mechanisms of BBB/BRB biology as it relates to development, function, imaging and disease. In contrast to similar meetings in the field of cerebrovascular biology or BBB organized by other non-profit organizations that have historically focused on more physiological and pharmacological aspects of the BBB, this meeting emphasizes modern approaches including cellular, molecular, transcriptomics, genetic, imaging and various model organisms, to dissect distinct aspects of BBB/BRB biology in healthy and diseased central nervous system (CNS). Topics to be discussed for the 2019 meeting will include: i. Development and Maturation of CNS Barriers; ii. Imaging and Function of the BBB/BRB in Health and Disease; iii. Model Systems to Study CNS Barriers; iv. Cell Biology of the BBB/BRB; v. Gene Therapy and Biotherapeutic Transport Across the BBB/BRB; vi. The Gut-Brain Axis and Neuroimmune Mechanisms. Given recent fundamental discoveries in the BBB/BRB field and blood-CSF barrier and the diverse approaches and model systems currently employed to understand CNS barriers biology, communication among international researchers is essential to continue to advance the research in this area since BBB/BRB impairment is a common feature of many neurological diseases, including brain trauma, stroke, tumors, autoimmune, ocular and neurodegenerative disorders and therefore this topic is highly relevant for the human health. Each session will be chaired by two leading scientists in the respective topic one of which is a senior and the other a more junior investigator. Selected speakers will include 1-2 senior invited speakers as well as graduate students, postdoctoral fellows and junior faculty selected from the list of submitted abstracts. One keynote lecture presented at the beginning of the meeting will provide an overview of the field and the critical background to stimulate discussion among scientists working on related but distinct areas of BBB/BRB biology. There will also be one poster sessions where the majority of participants will present their work and one power hour to address the challenges that women and minorities face in science, provide support for the professional growth of women and minorities in STEM careers and provide advice for science careers. Three posters will be selected for a prize of which the first and second will be presented as late breaking talks. The meeting will be of moderate size, as it has grown steadily from its inception in 2008. We anticipate >150 participants, including a significant number of students and postdoctoral fellows.

PROJECT NARRATIVE The blood vessels of the central nervous system (CNS) possess unique properties, termed the blood-brain barrier (BBB) or blood-retina barrier (BRB), that control the transport of nutrients and toxins between the CNS and blood critical for proper function of neurons and glial cells. The BBB/BRB also limits the entry of the immune cells and circulating antibodies into the CNS. BBB/BRB impairment is a common feature of many neurological diseases, including brain trauma, stroke, tumors, autoimmune and neurodegenerative disorders, that promotes the entry of immune cells and serum proteins into the CNS, neuroinflammation and neuronal dysfunction/death. Yet, BBB/BRB provides an obstacle to drug delivery in many neurological and psychiatric diseases. This conference of international scientists will meet to discuss the latest research in our understanding of the cellular and molecular mechanisms that regulate BBB/BRB function in health and disease and approaches to either repair the barrier in diseases characterized by neurovascular dysfunction or deliver therapeutics to the brain.