Key Dates

Related Announcements

PAR-22-201 - NIDA Program Project Grant Applications (P01 Clinical Trial Optional)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-184 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

PA-18-916 - AIDS-Science Track Award for Research Transition (R03 Clinical Trial Optional)

PAR-20-224 - Avenir Award Program for Research on Substance Use Disorders and HIV/AIDS (DP2 Clinical Trial Optional)

PAR-20-221- NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1, Clinical Trial Optional)

PA-20-187 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Required)

PA-20-188 - NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed)

PA-20-189 - NIH Pathway to Independence Award (Parent K99/R00 Independent Basic Experimental Studies with Humans Required)

PA-20-190 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)

PA-20-191 - Mentored Research Scientist Development Award (Parent K01 Independent Basic Experimental Studies with Humans Required)

PA-20-176 - Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required)

PA-20-208 - Substance Use/Substance Use Disorder Dissertation Research Award (R36 - Clinical Trials Optional)

PAR-19-345 - NIDA Program Project Grant Applications (P01 Clinical Trial Optional)

PAR-19-134 - Research Enhancement Award Program (REAP) for Health Professional Schools and Graduate Schools (R15 Clinical Trial Not Allowed)

PA-20-186 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Not Allowed)

PA-20-192 - Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Basic Experimental Studies with Humans Required)

Issued by

National Institute on Drug Abuse (NIDA)

Purpose

Purpose:

This Notice of Special Interest [NOSI] is to support computational HIV/AIDS research as it relates to NIDA’s mission through collaborative research between investigators with experimental expertise related to HIV/AIDS and those with computational proficiency, including scientists from statistics, physics, mathematics, engineering, and computer science. The NOSI will support meritorious and innovative research built on well-established computational strategies (theory, models, and methods) to investigate HIV-related neurocognitive deficits and neuropathogenesis in the context of substance use or substance use disorder (SUD). Investigators are expected to have complementary and integrated expertise in their field(s), but an ongoing collaboration or record of co-authorship is not required.

Background:

Substance use occurs more frequently in the HIV+ population than in the general population and is a major contributor to the persistence and the occurrence of HIV/AIDS cases. In comparison to non-drug users, HIV+ patients with comorbidity of substance use and SUD often have exacerbated or accelerated immune imbalance and cognitive/behavior deficits, representing added challenges to host immune status, defense mechanisms, and responses to foreign insults. In addition, emerging consensus indicates that SUD may modulate various stages of the HIV life cycle (e.g., increasing cell susceptibility to infection, promoting viral transcription, and depressing immune responses to virally-infected cells) that would impact persistence (rebound, reservoir, and eradication) of HIV after ART.

Computational approaches offer novel tools and theories that may shed light on how complex high-level phenomena emerge from interactions at smaller scale levels. For example, approaches that involve whole brain modeling or consideration of complex systems are likely to illuminate brain network-level mechanisms underlying clinical deficits. In general, computational neuroscience provides a theoretical foundation and a rich set of technical approaches to model and analyze data about interactions within and across multiple domains, physiological systems, and disease conditions, the emergent properties of large numbers of individual elements, as well as the appropriate choice of the involved time scales in terms of short-term to long-term changes. The integration of cutting-edge statistical methods and mathematical optimization in the neurosciences has the capacity to drive and convert complex scientific findings into knowledge by improving the accuracy of brain measurements such as calcium imaging and fMRI, quantifying uncertainty of estimates, and explaining variability in data. Moreover, artificial intelligence-based approaches facilitate mining large data sets, categorizing brain dysfunction in a way that has the potential to lead to better diagnoses, treatment, and cure in people with HIV. This integrated approach of computational neuroscience has the power to discover predictors of HIV disease progression that are specific to SUD patients. This could guide the development of disease progression and prognosis predictors, and therapeutic approaches tailored to correct the neural, cognitive, inflammatory and immune imbalances associated with substances of abuse.

Collaborative research in this area plays a pivotal role, enabling close interaction between theory, modeling, simulation and analysis, and experimental neuroscience. Theory coupled with mathematical modeling and simulations are needed to identify gaps in knowledge, to drive the systematic collection of the future data, and to formulate testable hypotheses. Statistical approaches are needed to conduct formal inference to support or refute a stated theory or hypothesis. Finally, new data analysis methods are needed to detect features and patterns in complex data, often spanning multiple modalities and scales. This provides a framework for development of quantitative hypotheses for empirical testing, combined with interpretation of data and formulation of new theoretical models that are grounded in empirical neuroscience. Further, sharing of data, software, and other resources provides a powerful modality for larger-scale interaction and collaborative discovery.

Research Objective:

Applications responsive to this NOSI should build on well-established computational strategies (theories, models, and methods) to understand HIV neuropathogenesis, and underlying complex neurobiological systems in the context of substance use and SUD.

Projects are encouraged to include close collaboration between quantitative and experimental researchers with expertise in HIV/AIDS and SUD neuroscience, including scientists from statistics, physics, mathematics, engineering, and computer science. It is expected that: (1) research collaborations will build on complementary investigator expertise in computation or modeling, theory, and/or experimental neuroscience; (2) the development and testing of new models or theories should provide a framework for the design of experiments and the generation of new hypotheses that can help reveal mechanisms and processes underlying HIV-related neurocognitive deficits and neuropathogenesis in the context of substance use or SUD; (3) the data generated from these projects are expected to be made findable, accessible, interoperable, and reusable (FAIR) to enable secondary analysis by the research community; and (4) any computational tools developed under this NOSI should be made widely available to the neuroscience research community for their use and modification.

Topics of interest include, but are not limited to:

1. Illuminating and classifying homeostatic mechanisms of persistent inflammation, neuroimmune interactions, and plasticity of neural-cognitive-behavior function influencing pathogenesis and heterogeneity in neuroHIV comorbidity
2. Identifying molecular biomarkers and/or targets relevant to the status, breadth, or kinetics of disruption of HIV-related neurocognitive deficits or neuropathogenesis in the context of substance use or SUD (Some host characteristics of interest include immune or defense mechanisms, genetic determinants, molecular and genomic pathways, or cellular or brain circuitry neurosignatures)
3. Systems biology study of mechanisms and factors within and between multi-scale biological networks in the face of HIV-related perturbation of intrinsic system integrity
4. Statistical models for HIV-associated cognitive decline in SUD
5. Quantitative analysis and computational modeling of viral rebound in substance exposed animals
6. Computational models of neural circuit dysfunction that take into account individual differences such as genetic makeup, cognitive function, psychiatric profile and personality features in the context of neuroHIV
7. Secondary analysis of large HIV datasets towards the development of improved biomarkers, including artificial intelligence approaches
8. Integrating and performing meta-analysis of all datasets across all cohorts and physiological systems to define generalizable mechanisms that underlie the impact of the different substances of abuse on HIV persistence, immune homeostasis and function, and neurocognitive dysfunction.
9. Applying simulation-based approaches towards understanding whole brain dynamics related to neuroHIV and SUD comorbidity
10. Development of statistical methods for neuroHIV study that draw upon established toolset to enhance the accuracy of brain signal measurements.
11. Computational models that will differentiate etiological factors underlying heterogeneity of neuroHIV and SUD comorbidity
12. Identification of biomarker, signatures or computational markers that will define level of risk propensity seeking addictive substances or will reflect/represent quantitatively the level of disruption or addiction which is commonly affected under the influence of specific drugs or poly-drug use and under different phase or various type of addiction.

Applicants should consider the following in preparing research applications responsive to this announcement:

1. Apply causality design when scientifically feasible to illustrate specific processes linking substance use or SUD to HIV-associated perturbation.

2. Variables selected for analysis should be justified based upon well documented relevance to HIV-induced deteriorations and complications. For example, tests of attention or memory assessment should be relevant to HIV-associated pathogenesis.

3. Projects submitted in response to this NOSI MUST include expertise and resources in areas of HIV/AIDS, SUD, and computational methods/data science. The collaborators are expected to have complementary and integrated expertise and demonstrated accomplishments in their field(s). However, an ongoing collaboration or record of co-authorship is not required.

Application and Submission Information

This notice applies to due dates on or after October 5, 2021 and subsequent receipt dates through January 8, 2025

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice:

• PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-184- Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
• PA-20-183- Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-194- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
• PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-20-196- NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)
• PA-18-916 - AIDS-Science Track Award for Research Transition (R03 Clinical Trial Optional)
• PAR-20-224- Avenir Award Program for Research on Substance Use Disorders and HIV/AIDS (DP2 Clinical Trial Optional)
• PAR-20-221- NIDA Avant-Garde Award Program for HIV/AIDS and Substance Use Disorder Research (DP1, Clinical Trial Optional)
• PA-20-187- NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Required)
• PA-20-188- NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Not Allowed)
• PA-20-189- NIH Pathway to Independence Award (Parent K99/R00 Independent Basic Experimental Studies with Humans Required)
• PA-20-190- Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)
• PA-20-191- Mentored Research Scientist Development Award (Parent K01 Independent Basic Experimental Studies with Humans Required)
• PA-20-176- Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required)
• PA-20-208- Substance Use/Substance Use Disorder Dissertation Research Award (R36 - Clinical Trials Optional)
• PAR-19-345- NIDA Program Project Grant Applications (P01 Clinical Trial Optional)
• PAR-19-134- Research Enhancement Award Program (REAP) for Health Professional Schools and Graduate Schools (R15 Clinical Trial Not Allowed)
• PA-20-186- Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Clinical Trial Not Allowed)
• PA-20-192- Midcareer Investigator Award in Patient-Oriented Research (Parent K24 Independent Basic Experimental Studies with Humans Required)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-DA-22-030 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Yu (Woody) Lin,
{Division of Neuroscience and Behavior
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1318
Email: ylin1@mail.nih.gov

Vani Pariyadath,
Division of Neuroscience and Behavior
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1318
Email: vani.pariyadath@nih.gov

Susan Wright
Division of Neuroscience and Behavior
National Institute on Drug Abuse (NIDA)
Telephone: 301-435-1318
Email: susan.wright@nih.gov