Notice of Special Interest (NOSI): Exploring the Roles of Biomolecular Condensates (BMCs) in Substance Use Disorder and/or HIV-related processes

Notice Special Interest NOSI): Exploring Roles Biomolecular Condensates BMCs) Substance Disorder and/or HIV-related processes Notice Number: NOT-DA-20-018 Key Dates Release Date: March 25, 2020 First Available Due Date: June 05, 2020 Expiration Date: September 08, 2023 Related Announcements PA-19-056: NIH Research Project Grant Parent R01 Clinical Trial Allowed) PA-19-091: NIH Research Project Grant Parent R01 Basic Experimental Studies Humans Required) PA-19-052: NIH Small Research Grant Program Parent R03 Clinical Trial Allowed) PA-19-053: NIH Exploratory/Developmental Research Grant Program Parent R21 Clinical Trial Allowed) PAR-18-437: Cutting-Edge Basic Research Awards CEBRA) R21-Clinical Trial Optional) PA-18-591: Administrative Supplements Existing NIH Grants Cooperative Agreements Parent Admin Supp - Clinical Trial Optional) Issued National Institute Drug Abuse NIDA) Purpose purpose this Notice to inform potential applicants the National Institute Drug Abuse NIDA) special interest research examining roles biomolecular condensates BMCs) their regulators processes relevant substance disorders SUDs) and/or HIV infection, latency, pathogenesis. Background Biomolecular condensates BMCs) diverse dynamic subcellular domains formed liquid-liquid phase transitions which multivalent proteins, RNAs, proteins intrinsically disordered regions IDRs) nucleate subcellular regions a distinct liquid phase aqueous solution. BMCs previously unrecognized important roles a wide variety biological processes including regulation gene expression, organization subcellular structures the nucleus cytosol, clustering neurotransmitter-containing synaptic vesicles voltage gated calcium channels the synapse. Recent work indicates multiple proteins implicated neurodegeneration associated pathological protein aggregation also participate the formation BMCs. is emerging evidence dendritic spines synapses utilize BMCs their formation dynamics. Additionally, is recently discovered role BMCs modulation receptor kinase signaling membranes. CNS BMCs Substance Disorders.Much remains be learned the role BMCs their regulators CNS functions including chromatin structure, gene expression, dendritic spine formation, synaptic function, neurodegeneration, regeneration, subcellular localization channels, receptors, vesicles. Addictive substances impact of processes could influence CNS functions part via BMCs. Although role BMCs receptor kinase signal transduction the plasma membrane been established, is known whether BMCs influence GPCR signal transduction, BDNF receptor function, the functions other signal transduction pathways relevant addictive substances. BMCs HIV.There much do know BMCs HIV biology. example, has recently shown vesicular stomatitis virus VSV) exploits nuclear BMC efficient replication the VSV RNA genome, it not known HIV uses BMC a similar purpose. Despite emerging role BMCs establishing regulating chromatin structure the nucleus, little known the potential involvement BMCs HIV/SIV infection, formation maintenance HIV latency whether HIV latency be strengthened diminished manipulation nuclear BMCs. Dysregulation BMC-related processes also be involved the etiology HIV-associated Neurocognitive Disorder HAND). Research Objectives purpose this NOSI to encourage submission research projects examining roles BMCs their regulators processes relevant SUDs and/or HIV infection, latency, pathogenesis. is anticipated compelling projects require interdisciplinary collaborations between individuals expertise BMCs with significant knowledge substance and SUDs and/or HIV infection, replication, latency, pathogenesis. Applicants encouraged establish such collaborations. is anticipated investigations the role BMCs substance or SUD-relevant processes HIV infection, replication, latency, pathogenesis uncover potentially novel mechanistic insights. addition, work this area yield potentially new unexpected targets could exploited treat SUDs, HIV, HIV-related pathological consequences. examples research projects appropriate this NOSI include, are limited to: SUD-relevant Development technologies improve identification, monitoring, manipulation BMCs BMC regulators including RNAs proteins involved BMC formation, dissolution, composition) SUD-relevant cell types models. Exploration the role BMCs BMC regulators SUD-relevant processes, cells, models including pre-synaptic function, post-synaptic function, vesicular regulation, RNA transport, neuronal plasticity, CNS development, neural growth factors, functions non-neuronal CNS cell types. Exploration the roles BMCs opioid, cannabinoid, nicotinic, dopaminergic, other signaling gene expression pathways relevant addictive substance use. Testing role BMCs addictive processes using animal models exposure addictive substances including nicotine, cocaine, methamphetamine, stimulants, opioids, prescription drugs, cannabinoids, alcohol, combinations these drugs. silicoor high throughput screening approaches identify BMC proteins their regulators might function SUD-relevant signal transduction influence functions SUD-relevant receptors, channels, other signal transduction components. Investigation nuclear BMCs their regulators SUD-relevant gene expression chromatin regulation. nuclear BMCs be involved regulation chromatin structure, nuclear bodies, transcription, splicing, other nuclear processes. Approaches develop novel ways manipulate SUD-relevant BMCs BMC function through pharmacological, genetic, targeting, other strategies. HIV-relevant Development technologies improve monitoring and/or manipulation BMCs BMC regulators HIV/SIV infected latent cells. Exploration the role BMCs BMC regulators HIV/SIV related processes including infection, replication, latency formation maintenance, pathogenesis, neurodegeneration e.g. HAND). silicoor high throughput screening approaches identify HIV-relevant host viral components BMCs their regulators. Investigation nuclear BMCs their regulators HIV/SIV infection, replication, latency, treatment, pathology. nuclear BMCs be involved regulation chromatin structure, nuclear bodies, transcription, splicing, other nuclear processes. Investigation BMCs T cell function how functions might impact HIV/SIV replication latency. Investigation changes CNS BMCs their regulators response HIV/SIV HIV therapies. Phenotypes might include morphological functional changes CNS cells, subcellular structures, dendritic spines, synapses. Approaches develop novel ways manipulate HIV-relevant BMCs BMC function through pharmacological, genetic, targeting, other strategies. Projects investigating role BMCs regulation signal transduction pathways relevant HIV. SUD HIV-relevant Exploration BMCs their regulators biological processes impacted both HIV/SIV addictive substances the CNS immune system. of artificially engineered BMCs deliver therapies otherwise treat SUDs HIV. Application Submission Information notice applies due dates or after June 5, 2019 subsequent receipt dates through September 8, 2023. Submit applications this initiative using of following funding opportunity announcements FOAs) any reissues these announcement through expiration date this notice PA-19-056: NIH Research Project Grant Parent R01 Clinical Trial Allowed) PA-19-091: NIH Research Project Grant Parent R01 Basic Experimental Studies Humans Required) PA-19-052: NIH Small Research Grant Program Parent R03 Clinical Trial Allowed) PA-19-053: NIH Exploratory/Developmental Research Grant Program Parent R21 Clinical Trial Allowed) PAR-18-437: Cutting-Edge Basic Research Awards CEBRA) R21-Clinical Trial Optional) PA-18-591: Administrative Supplements Existing NIH Grants Cooperative Agreements Parent Admin Supp - Clinical Trial Optional) instructions the SF424 R&R) Application Guide and funding opportunity announcement used submission must followed, the following additions: funding consideration, applicants must include ldquo;NOT-DA-20-018” without quotation marks) the Agency Routing Identifier field box 4B) the SF424 R&R form. Applications without information box 4B not considered this initiative. Applications nonresponsive terms this NOSI be be considered the NOSI initiative. nbsp; Inquiries Please direct inquiries the Scientific/Research, Peer Review, Financial/Grants Management contacts Section VII the listed funding opportunity announcements. Scientific/Research Contact(s) John Satterlee, Ph.D. National Institute Drug Abuse NIDA) Telephone: 301) 435-1020 Email: satterleej@nida.nih.gov Peer Review Contact(s) Examine eRA Commons account review assignment contact information information appears weeks after submission due date). Financial/Grants Management Contact(s) Aida Vasquez National Institute Drug Abuse NIDA) Telephone: 301-480-2154 Email: vasquez@mail.nih.gov nbsp; nbsp;