Notice Number: NOT-GM-19-054

Key Dates
Release Date: July 29, 2019

Issued by
National Institute of General Medical Sciences (NIGMS)

Purpose

The purpose of this notice is to inform potential applicants to the National Institute of General Medical Sciences (NIGMS) of areas of sepsis research that are of special interest to the Institute. NIGMS is interested in receiving applications that will provide new knowledge of the mechanistic complexity of sepsis in humans and that will test strategies for translating this knowledge into improved diagnostics and therapies for sepsis patients.

Background

Despite decades of intensive study, sepsis remains a poorly understood condition with limited diagnostic tools and few specific treatments. A working group of the National Advisory General Medical Sciences Council (NAGMSC) was convened to advise NIGMS on how to optimize its research grant support of preclinical and clinical sepsis studies to most effectively provide fundamental knowledge of human sepsis and to enable translation of this knowledge into improved diagnostic tools and therapies.

Based on the recommendations of the NAGMSC Sepsis Working Group and consistent with its mission, NIGMS intends to continue its support of fundamental discovery science (basic and clinical) relevant to understanding the mechanisms that underlie the heterogeneity that is associated with the pathogenesis and resolution of sepsis in humans. NIGMS will explore the possibility of providing support that will enable access to biospecimens and data from septic patients for research purposes. NIGMS will also coordinate with other NIH institutes and government agencies to enable efficient clinical testing of new diagnostics and treatments for sepsis.

Research Objectives

NIGMS seeks to support sepsis research that uses new and emerging approaches, such as clinical informatics, computational analyses, and predictive modeling in patients, and new applications of high-resolution and high-throughput bioanalytical techniques to materials obtained from septic patients. Observational studies of septic patients that are designed to provide new knowledge of the biological mechanisms that are associated with the clinical heterogeneity of disease and resolution processes are strongly encouraged. NIGMS also has an interest in studies that explore the use of research organisms that have not traditionally been employed as models for understanding sepsis. Development of novel tools and technologies for sepsis research, detection, and treatment is encouraged.

Specific topics of research interest include, but are not limited to the following:

• Understanding the pathophysiology, treatment responses, clinical trajectories, initial resolution, and long-term outcomes of sepsis patients at various levels of biological organization (molecule, cell, tissue, organism, etc.)
• Identifying, classifying, and stratifying sepsis patients rapidly and accurately in various care settings
• Mechanistic studies using patients, patient-derived materials, or clinical data sets that will enable future development of diagnostic or treatment modalities
• Use of clinical data such as that from electronic health records to develop predictive diagnostic algorithms or to provide understanding of patient heterogeneity and treatment responses
• Multidisciplinary team approaches focused on development of new strategies for sepsis detection and diagnosis, patient stratification, and treatment
• Analytical approaches that combine different types of data such as molecular and clinical to functionally define sepsis subgroups or endotypes
• Identification, characterization, and validation of sepsis-specific biomarkers particularly in the context of enabling endotyping strategies or future evaluation of diagnostics and novel therapies
• Studies that explore how genetic determinants, biological variables (sex, age, underlying health conditions), or other relevant population characteristics (race, ethnicity, socioeconomic status) are associated with differences in sepsis endotypes, treatment responses, clinical trajectories, resolution, and/or long-term outcomes
• Application of cutting-edge data science approaches such as artificial intelligence and machine learning to fundamental and clinical sepsis research questions
• Integration of discovery approaches such as genomics, proteomics, lipidomics, metabolomics, etc. to elucidate the molecular basis of the pathophysiology and resolution of sepsis and to molecularly define sepsis subgroups in humans
• Mechanistic research employing non-traditional models to discern pathways that contribute to the complex and disparate responses that are associated with the pathophysiology and resolution of sepsis in humans
• Basic and clinical studies that examine non-immunological contributions to sepsis
• Development of new assays and technologies that will enable efficient use of sepsis biospecimens by researchers and clinicians
• Application of new research methods and models such as in silico approaches, cell culture, and organoids to early-stage testing and validation of potential sepsis diagnostics and therapeutics
• Early stage research and development projects through the NIH SBIR/STTR program to create commercializable tools or technologies for sepsis research, detection, or therapy

NIGMS considers the following areas to be of low priority:

• Studies using rodent models of sepsis unless uniquely well-justified in terms of potential for providing novel insights into human sepsis
• Clinical trials: In general, NIGMS will only consider support of clinical trials that are designed to test strong mechanistic hypotheses and include appropriate patient stratification. NIGMS expects the scientific foundation of all clinical trial applications to be based on data from rigorously designed and controlled human studies that have been published in peer-reviewed literature. NIGMS is unlikely to support large-scale clinical trials unless other NIH institutes/centers or federal agencies provide joint support to optimize trial efficiency, recruitment, and oversight.

Application and Submission Information

Applications in response to this Notice may be submitted through any active NIGMS Funding Opportunity Announcement. All instructions for the selected Funding Opportunity Announcement must be followed.

Investigators planning to submit an application are strongly encouraged to discuss their proposed research with the scientific contact listed below well in advance of the application due date.

Inquiries

Please direct all inquiries to:

Xiaoli Zhao, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Email: xiaoli.zhao@nih.gov