Development, Integration, and Data Mining of Biomolecular and Cellular Networks for Discovering Druggable Targets for Alcohol Use Disorder and Alcohol-Induced Organ Damage

Notice Number: NOT-AA-17-007

Key Dates
Release Date:   June 27, 2017

Related Announcements
None

Issued by
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Purpose

This NIH Guide Notice is to encourage the use of biomolecular and cellular networks to better understand the mechanisms underlying Alcohol Use Disorder (AUD) and alcohol-induced organ damage (AIOD) and to identify potential therapeutic targets for treating AUD and AIOD. Traditionally, drug discovery has hinged on selecting “one target, one drug.” To increase the likelihood of developing a greater number of efficacious medications and identify more effective druggable targets, complementary approaches are needed. Network pharmacological and system genomics approaches enable us to incorporate, integrate, and prioritize “multiple targets, multiple drugs” in a single concerted way. This may offer significant advantages over traditional approaches to drug discovery.
Several types of biomolecular networks are known to exist, such as gene-gene interactive networks, gene-protein networks, protein-protein interaction networks, metabolic networks, and regulatory networks, including non-coding RNA networks that influence overall genomic function. These biomolecular networks have been identified using multidisciplinary approaches, including bioinformatics, systems biology, network biology, cheminformatics, and pharmacology. Such networks can be very powerful and can assimilate large amounts of data, especially from genomics, epigenomics, transcriptomics, proteomics, and metabolomics data sets. Moreover, because such biomolecular and cellular networks are dynamic in nature, modeling needs to be active and ever-changing to increase the validity of these networks. Finally, given their vital role, these networks should help to identify mechanisms underlying AUD and AIOD and new druggable targets, mainly proteins, genes, and RNAs.

Research Interest

NIAAA encourages researchers to use existing programs (e.g., NIH Common Fund: https://commonfund.nih.gov/) to develop and integrate biomolecular and cellular networks toward discovering new, effective targets and target combinations and subsequent candidate compounds (both novel and repurposing compounds) to treat AUD and AIOD.  This effort blends informatics with biological understanding of the mechanisms surrounding AUD and AIOD to give a more complete understanding of how a particular medication might work and to identify subgroups of people who might benefit the most from that medication. Because such biomolecular and cellular networks are dynamic in nature, dynamic modelling of these networks should be considered.

Inquiries

Please direct all inquiries to:

Hemin Chin, PhD
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-594-1282
Email:  chinh@mail.nih.gov

Dale Hereld, MD, PhD
Division of Metabolism and Health Effects
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-0912
Email:  hereldd@mail.nih.gov