{"591164":{"#nid":"591164","#data":{"type":"event","title":"When the Same Genotype Leads to Multiple Phenotypes: Measuring and Manipulating Partial Penetrance Underlying Disease","body":[{"value":"\u003Cp\u003E\u003Cstrong\u003EAbstract:\u003C\/strong\u003E\u003Cbr \/\u003E\r\nWhen a genotype is partially penetrant, not all individuals in an isogenic population display the same phenotype. \u0026nbsp;This effect is seen widely across biology: genetics are only a modest predictor of disease for monozygotic twins; only a fraction of cells during cellular reprogramming become pluripotent; mutations lead to cancer in only a fraction of cases.\u0026nbsp; Partial penetrance is often difficult to measure, hard to target therapeutically, and its underlying mechanisms remain unclear.\u0026nbsp; Here I demonstrate that retroviruses, such as HIV, provide an excellent system to study penetrance.\u0026nbsp; HIV integrates semi-randomly across the genome and, as we\u0026rsquo;ve recently shown (\u003Cstrong\u003E\u003Cem\u003ECell\u003C\/em\u003E\u003C\/strong\u003E 2015), initiates a program of probabilistic fate-choice between active replication or transcriptionally-silent \u0026lsquo;latency\u0026rsquo;. \u0026nbsp;The latent virus can stochastically switch to active replication, obligating patients to take antiretroviral drugs for life.\u0026nbsp; This partially penetrant behavior of latent-or-active switching is the primary barrier to curing HIV-AIDS.\u0026nbsp; In my research, I take advantage of the fact that viral fate is sensitive to its genomic location and repurpose it as a genome-wide probe. \u0026nbsp;I will describe methods to measure viral fate switching across genomic sites through next-generation sequencing and time-lapse microscopy. \u0026nbsp;From a therapeutic perspective, I will discuss how these measurements enable computational identification of latency-reversing drugs.\u0026nbsp; From a cellular perspective, the measurements provide a probabilistic map of transcription across the genome.\u0026nbsp; This quantifies transcriptional traits of sites such as leakiness, inducibility, or constitutive behavior \u0026ndash; information that is immediately relevant in picking safe harbors for genetic engineering.\u0026nbsp; Broadly, measuring how specific genetic features enhance or suppress viral fate switching reveals how these features function natively and how they may be targeted when associated with disease.\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"Seminar by Anand Pai, University of California San Francisco"}],"uid":"27964","created_gmt":"2017-05-01 16:54:17","changed_gmt":"2017-05-01 16:54:17","author":"Jasmine Martin","boilerplate_text":"","field_publication":"","field_article_url":"","field_event_time":{"event_time_start":"2017-05-04T16:00:00-04:00","event_time_end":"2017-05-04T17:00:00-04:00","event_time_end_last":"2017-05-04T17:00:00-04:00","gmt_time_start":"2017-05-04 20:00:00","gmt_time_end":"2017-05-04 21:00:00","gmt_time_end_last":"2017-05-04 21:00:00","rrule":null,"timezone":"America\/New_York"},"extras":[],"groups":[{"id":"1278","name":"College of Sciences"},{"id":"1275","name":"School of Biological Sciences"}],"categories":[],"keywords":[{"id":"168156","name":"Steve Diggle"},{"id":"174282","name":"Anand Pai"},{"id":"166892","name":"School of Biological Sciences Seminar"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[{"id":"1795","name":"Seminar\/Lecture\/Colloquium"}],"invited_audience":[{"id":"78761","name":"Faculty\/Staff"},{"id":"78771","name":"Public"},{"id":"174045","name":"Graduate students"},{"id":"78751","name":"Undergraduate students"}],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}