R35GM139382: Advanced Computational Modeling of Molecular Machines in Gene Regulation and DNA Repair

R35GM139382: Advanced Computational Modeling of Molecular Machines in Gene Regulation and DNA Repair is sponsored by National Institute of General Medical Sciences (NIGMS), NIH. This grant supports advanced computational modeling of molecular machines involved in gene regulation and DNA repair.

Contacts by Research Area | National Institute of General Medical Sciences NIGMS encourages all potential applicants to talk to a program officer before preparing and submitting an application. Find contact information for the program officer overseeing grants in your scientific area of interest, desired training program, or capacity building initiative below.

​ Biophysics, Biomedical Technology, and Computational Biosciences Bioinformatics and Computational Biology Genetics and Molecular, Cellular, and Developmental Biology Developmental and Cellular Processes Pharmacology, Physiology, and Biological Chemistry Physiology and Clinical Sciences Biochemistry and Molecular Pharmacology Chemistry and Chemical Biology Research Capacity Building Institutional Development Award (IDeA) Health Research Programs for Federally-Recognized Tribes Support for Research Excellence (SuRE) Biomedical Research Environment & Sponsored Programs Administration Development (BRE-SPAD) Training and Workforce Development Cross-Disciplinary Pathway Programs (CPP) Discipline Specific Training (DST) Postdoctoral, Early Career, and Workforce Development Biophysics, Biomedical Technology, and Computational Biosciences Bioinformatics and Computational Biology Branch Development of computational and informatics tools and methods for data privacy, harmonization, integration and analysis using electronic health records and other biomedical data aimed at elucidating biological function, ontology development, or developing models of biological and biochemical processes.

Areas of interest include population pharmacokinetics, pharmacovigilance, drug discovery and drug repurposing. Development of algorithms and computational tools for collecting, managing, analyzing, visualizing, and interpreting complex biomedical data; or using data science methods and tools to extract and discover new knowledge about biological systems.

The scope of studies includes the development of computational algorithms to analyze data from nucleic acid sequencing, proteomics, metabolomics, and multi-omics, and development of methods for large scale data management including data curation, standardization, and ontology. Development of advanced statistical techniques and methodologies for study design, data analysis and interpretation.

The scope of studies ranges from those focused-on sequencing, -omics, bioimaging, high-through-put technologies in molecular and cellular biology data, pharmacology, and populational studies. Algorithm design and software development for bioinformatics research.

The scope of studies includes software and tools development to facilitate biological data analysis, interpretation, and visualization to address research questions in basic biology. Areas of interest include software to analyze cellular processes and interactions and software engineering for ontology and data structure.

Development of new computational algorithms and mathematical methods for integrative understanding of biological systems that may span temporal and spatial domains. The system scale ranges from subcellular to cellular to tissue, organ, organoids/3D cultures, and organismic systems.

Topics include cellular regulatory processes such as gene expression and metabolism, cellular architecture and intracellular dynamics, cell communication and motility, cell division and differentiation, tissue formation, organogenesis, and tissue and organ functions.

Infectious Disease Modeling Development of computational modeling for understanding population dynamics related to the interaction of organisms with their physical environment and between species. In this context, infectious disease models are used to understand the spread of parasites, viruses, and infectious diseases.

Technologies for Structural Biology Development of new or improved instruments, methods, and related software to elucidate 3D structures of macromolecules and macromolecular complexes.

Relevant technologies cover areas of sample handling; X-ray diffraction and other X-ray techniques; magnetic resonance techniques such as NMR, EPR, and ESR; microscopic techniques that resolve at the molecular level such as single particle cryo-electron microscopy, micro electron diffraction (micro-ED) and tomography (cryo-ET); computational tools for data collection, processing, interpretation, curation, and mining.

Bioanalytical Technologies Development of new or improved techniques, instruments, tools, or methods for quantitative analyses of biomolecules such as proteins, carbohydrates, lipids, nucleic acids, metabolites, and complexes.

Technologies and methods development areas include mass spectrometry; magnetic resonance technologies; surface plasmon resonance; optical and vibrational spectroscopy; sample handling and separations; labeling methods; microfluidics, flow-based systems; high-throughput techniques; biosensors and electrochemical tools; and associated computational tools for data mining, analysis, interpretations, -omics, and simulation of molecular dynamics.

Carolina Salvador Morales, Ph. D. Technologies for Microscopy and Imaging Development of new or improved laboratory/experimental techniques, instruments, or supporting software that measure the location and dynamics of molecules in situ, and organelles, cells, or tissues on the nanometer and micrometer length scales.

These include instrument design; development of integrative multiscale or multimodal approaches for measuring cell structure and function; new illumination/excitation sources and detectors of heat, sound, light, electrons, and X-rays; imaging modes of spectroscopy; development of particles, physiochemical or mechanical probes; computational approaches to image formation including super-resolution microscopy and tomography; image analysis and processing algorithms of image sets for data interpretation, curation, mining, and visualization; development of sample preparations and modifications for imaging; probes, molecular reporters and fluorescent indicators for structural or functional imaging or microscopy/nanoscopy.

Technologies for Investigating and Manipulating Cells Development of new or improved tools and methods that directly manipulate or investigate the properties of cells and their environment.

These include the development of methods for the design and delivery of molecules and nanoparticles into cells or transport between cellular compartments, such as electroporation, co-transporters, or partitioning; tools for cell engineering or direct measurement of cell function; development of biological, chemical, or physical assays for measuring the function of macromolecular complexes within the cellular milieu, the behavior of organelles, or for characterizing cell phenotype.

Carolina Salvador Morales, Ph. D.

Molecular Modeling, Theory, and Design Includes theoretical, computational, and physics-based studies of the fundamental behaviors of atoms to molecules and their interactions, including predominantly theoretical and computational studies in the following areas: quantum mechanical and molecular dynamics simulations; thermodynamics and statistical mechanics; basic principles of molecular recognition; development and validation of force fields and scoring functions; and algorithms for prediction of molecular properties; macromolecule-ligand binding predictions by docking and other in silico screening methods applicable to drug design; predictions of protein and other macromolecular structures; and studies in macromolecular design, protein folding, RNA folding, macromolecular dynamics, molecular interactions, membrane and membrane protein simulations, phase separation, aggregation, and complex formation.

Biophysics of Proteins – Folding, Interactions, Structure/Dynamics, Mechanisms Biophysical studies of all aspects of protein structure and function in which the goal is to elucidate general principles, including establishing the physical and thermodynamic basis for native structure; protein-protein interactions; protein-ligand recognition; folding mechanisms and kinetics; and protein de novo design and engineering.

Experimental studies of intrinsically disordered proteins; folding upon binding, protein aggregation, and phase separations. Included are studies of structural dynamics in protein function and allosteric control. Experimental methods may include confirmatory in vivo studies and/or established computational methods.

Biophysics of Nucleic Acids and Nucleoprotein Complexes Research involving the application of physical principles to the study of nucleic acids and protein-nucleic acid complexes.

Areas of research include physical and chemical studies on the structure of nucleic acids and protein-nucleic acid complexes; analysis of protein–nucleic-acid interactions and assembly mechanisms; ligand-nucleic acid interactions; development of physical, chemical, and theoretical/computational techniques for the analysis of nucleic acids and their complexes.

Biophysics of Membranes and Membrane Proteins General principles of membrane structure and function, including the behavior of lipids, bilayers, and other lipid phases; membrane protein structure and function, including folding, assembly, dynamics, and general mechanisms of action, conformational changes, and energy coupling; membrane protein-lipid interactions, effects of lipid compositions and phase separated domains; physical studies of fusion, fission, and deformation processes; as studied through the application of primarily biophysical methods and approaches.

Biophysical Studies of Supramolecular Complexes Research on the mechanisms of assembly, structure, and function of cellular ultra-structures larger than a few million Daltons and dependent on high levels of molecular organization.

These include large cellular machines such as the ribosome, spliceosome, cytoskeletal structures, interactions between intracellular and extracellular matrix components, signaling networks that depend on large-scale interactions when studied primarily by multiple methods and/or by methods that are not routine, such as single particle cryo-electron microscopy, cryo-electron tomography, scanning probe microscopy, and other force transduction methods.

Biophysical Studies of the Viral Life Cycle Research involving the application of physical principles to the study of viral attachment, fusion/penetration, uncoating, assembly, and budding/release.

Areas of research include analysis of virus-host interactions; phage and viral packaging; the structure and mechanism of assemblies from viral and host components; and determining factors and energetics that regulate protein-nucleic acid interactions necessary for virion entry, packaging, maturation, and release.

SBIR/STTR Program for BBCB This portfolio comprises SBIR/STTR projects of general interest to the Division of Biophysics, Biomedical Technology, and Computational Biosciences. These projects are notable for their general pertinence to basic science issues and broad applicability of the proposed developments. For information about NIGMS SBIR programs, email Eddie Billingslea, Ph.

D . NIGMS Resources and Centers BBCB manages Resource and Center programs that provide technologies to the Biomedical Research Community. Genetics and Molecular, Cellular, and Developmental Biology Cell Death, Autophagy, and Homeostasis Regulation of cell death pathways, autophagy, and maintenance of cellular homeostasis.

Areas of interest include macro and selective autophagy, apoptosis, necroptosis, and metabolic and protein homeostasis. Cell Migration and Adhesion Processes that control migratory cell behaviors. Examples include bacterial chemotaxis and adhesion-based mechanotransduction signaling mechanisms.

Alexandra Ainsztein, Ph. D. Cell Polarity, Organization, and Mechanics Establishment of cellular polarity and cell shape.

The study of biomechanical forces and processes. Examples include epithelial topogenesis, yeast bud site selection, cell protrusions, positioning of organelles, mechanotransduction, and cell shape changes. Cellular Protein Folding and Degradation The cellular physiology of chaperones, proteosomes, and protein quality control pathways.

Cellular responses and management of misfolded proteins, such as the unfolded protein response and other stress responses. Cellular Signaling in Growth Cellular decision processes and intracellular signaling pathway dynamics, growth initiation, proliferation, cell senescence, terminal differentiation, and sporulation. Endocytosis, Lysosomes, Related Organelles Processes that regulate endocytosis and the endo-lysosomal network.

Studies of the function and biogenesis of endosomes, lysosomes, and lysosome-related organelles, and how membranes and proteins are recycled. Mechanisms of Cell Division Investigations into the assembly of mitotic and meiotic spindle apparatus components. Areas of interest include kinetochore functions, spindle assembly checkpoints, centrosomes, and chromosome attachment and movement.

Membrane Biology and Organelle Biogenesis General studies of membrane biology. Examples include membrane biogenesis, protein targeting and anchoring, and nuclear import and export. Research on fat-related organelles (e.g. lipid droplets, peroxisomes) and studies of lipid homeostasis.

Motors, Filaments, and Transport Focus is on the cytoskeleton and cytoskeleton-associated proteins. Areas of interest include the transport of cargoes by motor proteins, and specialized cytoskeletal-based structures like cilia, eukaryotic flagella, and basal bodies. Alexandra Ainsztein, Ph.

D. Protein Processing and Export, Golgi, and ER The processing and intracellular trafficking of proteins for export and the biogenesis of the Golgi and endoplasmic reticulum. Developmental and Cellular Processes Chromosome and Nuclear Structures Structure, function, and regulation of chromosomes.

Examples include higher order chromosome architecture, telomeres, centromeres, and large-scale programmed genome rearrangements. Chromatin and Epigenetic Mechanisms Mechanisms of gene activation and repression.

Examples include roles of chromatin and large protein-DNA complexes; interactions of DNA with nonhistone proteins; epigenetic factors influencing gene expression such as histone modifications, chromatin remodeling, DNA methylation, position effects, imprinting, X-inactivation, and gene silencing.

Genetic, molecular, and/or genomic characterization of circadian rhythms and regulatory processes associated with circadian clock elements, sleep, and related behavioral and physiological phenomena, with an emphasis in non-human systems including invertebrates, plants, fungi, and bacteria. Regulation of early events in normal development prior to organ formation. Emphasis is on non-mammalian systems.

Examples of developmental processes include cell and tissue polarization, collective cell migration, pattern formation, and morphogenetic changes during gastrulation and body axis extension. NIGMS’s support of neurodevelopment ends at the initial morphogenesis of the neural tube; it does not include subsequent brain and spinal cord regionalization, nor neuronal subtype specification/diversification.

Focus here is on understanding signaling pathways underlying fundamental processes that drive early (pre-organogenesis) normal development, primarily using non-mammalian systems. Research should be predominantly focused on the signaling cascades involved in developmental patterning and morphogenetic events rather than on gene regulatory networks or biophysical/biomechanical and cell-level mechanisms.

Topics include but are not limited to growth factor/morphogen signaling networks, planar cell polarity signaling, cytoneme/airineme-based signaling and signaling during collective cell migration. Genetic, genomic and/or molecular characterization of simple and complex behaviors, with an emphasis on non-mammalian research organisms.

The research may directly address genetic mechanisms, or use genetic tools to understand molecular mechanisms underlying behavior. The focus is on neural function, not neural development. Microbiome, Biofilms, and Quorum Sensing The genetic, physiological, and ecological mechanisms governing relationships between microbes.

How the microbiota responds at the community, population, organismal, or molecular level to maintain homeostasis or responds to dysbiosis of the host. The focus of the research should be on the microbiota and not the host or organ system. Research to facilitate an understanding of the biology of pathogenic microorganisms, pathogenesis, and pathogen-host interactions may be more appropriate for other NIH Institutes or Centers (ICs).

Andrea Keane-Myers, Ph. D. Organismal Response to Environmental Stressors Investigations into pathways that underlie adaptive responses to fluctuating environmental conditions.

This includes phenotypic plasticity. How research organisms respond to nutrient availability, parasitism, temperature, oxygen levels, pH, light, gravity, antibiotics, toxins, or metal ions. Population Genetics and Evolution Genetics of natural and laboratory populations.

Evolutionary topics include genetic variation in complex traits in humans and research organisms, chromosome evolution, phenotypic evolution and speciation, evolution of development, host-pathogen evolution and other co-adapting systems. Also, statistical methods and mathematical models for evolutionary and population genetic analysis.

NIGMS does not support research on evolutionary development of organs or organ systems, nor studies of ecology outside of the Ecology and Evolution of Infectious Disease Program that is jointly offered with the National Science Foundation. Stem Cell Biology and Regeneration The basic biology, biochemistry, genetics, epigenetics, and cellular organization of stem cells.

Included are embryonic, germline, induced pluripotent, and tissue-specific stem cells from humans and research organisms. Emphasis is on pluripotency maintenance and self-renewal, properties that distinguish stem cells from differentiated cells, nuclear reprogramming of somatic cells, and regulation of asymmetric cell division of stem and progenitor cells.

Regeneration topics include genetic, molecular, and/or genomic regulation of tissue and organ regeneration in non-human systems, including plants, with a particular interest in non-mammalian research organisms.

Chromosomal and Genome Stability Mechanisms of genome instability, including large scale chromosomal changes, gross chromosomal rearrangements, and aneuploidy; effects of non-telomeric chromatin on chromosomal and genomic stability; mutational mechanisms, including base insertions, expansion via slippage/repetitive sequences, and transposition; maintenance of genome integrity during meiosis.

DNA Replication and Repair Enzymes and mechanisms of DNA replication and repair, including by both replicative and non-replicative mechanisms; replication stress and fork repair; regulation of DNA repair, including factors that favor the action of one repair pathway over another; replication through chromatin; transcription-induced DNA damage.

A gene regulatory network (GRN) is a set of genes, gene modifications or parts of genes, that interact in a coordinated manner with each other to control a specific cell function. Gene regulatory networks are involved in development, differentiation and responding to environmental cues. GRNs can act at the level of transcription, translation or a combination.

This portfolio includes research on the study of the networks and the interacting genes and regulators. mRNA Metabolism and Translational Control Structure, function, and metabolism of cytoplasmic mRNA. Control of gene expression at the level of translation, including RNA editing, mRNA stability, and nonsense-mediated decay.

The mechanics of protein synthesis. Areas of interest include synthesis, structure and function of components of the translation system, namely tRNA, rRNA, ribosomal proteins, and initiation and termination factors. Mechanisms of production and regulation of regulatory RNAs including siRNAs, microRNAs, piRNAs, CRISPR RNAs and related non-coding RNAs.

Function of regulatory RNA including effects on mRNA stability or translation. All manner of processing of RNA species including the full-range of RNA splicing mechanisms. Also, the formation, structure, function, and regulation of spliceosomal precursors and components, and intranuclear transport of RNA.

Investigations into the macromolecular interactions that mediate or regulate transcription. Included are strategies and techniques for identifying molecules and sequences involved in regulating transcription at a global level.

Pharmacology, Physiology, and Biological Chemistry Physiology and Clinical Sciences Anesthesia and Perioperative Pain Basic, translational, and clinical research in anesthesiology, as well as studies of pain in the perioperative period.

This may include studies focusing on: molecular pharmacology and mechanisms of action of local and general anesthetics; pharmacokinetics and pharmacodynamics of anesthetics; pharmacological effects of anesthetics on tissue, organ, and organ systems; mechanisms of adverse action and toxicity of anesthetics; underpinnings of anesthesia-induced unconsciousness and emergence from anesthesia; malignant hyperthermia as it relates to anesthesia; or mechanisms involved in acute pain or the transition to chronic pain following surgery, and resolution of postoperative pain.

Zuzana Justinova, M. D. , Ph.

D. Drug Metabolism, Transport, and Kinetics Research on generalizable principles of pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenomics (PG), as well as drug-drug, drug-nutrient, drug-microbiome interactions and consequent adverse effects.

Areas of interest include drug metabolizing enzymes, drug transporters (excluding nutrient and neurotransmitter transporters), the role of the gut microbiota in drug metabolism, studies to examine the impact of genetic variability on drug response, large-scale evaluation of information on drug pathways from studies using biobanks and electronic health records, and studies on developing and employing optimal technologies and tools (e.g., biomarkers, research organisms, and 3D tissue models) for PK/PD/PG studies.

Studies may include approaches to understand population pharmacogenetics, pharmacogenomics, physiologically based pharmacokinetic (PBPK) studies, and drug toxicity. NOTE: When the research is focused on a specific organ or organ system, disease or condition, it will likely fall within the mission of the appropriate categorical institute.

Injury and Critical Illness Research on total body responses to injury (traumatic, thermal, or surgical) and shock from post-injury period to acute phase through long-term effects, until recovery or mortality.

Studies on host response to injury and shock may include research on mechanisms of pathophysiological systemic responses (e.g., altered immune response, hypermetabolism, endotheliopathy/coagulopathy) or research on complications seen in critical care medicine (e.g., systemic inflammatory response syndrome, multiple organ dysfunction syndrome mechanisms and others).

NOTE: Studies focused on specific organs or conditions, such as traumatic brain injury, pathogenic infections, skin grafts, etc., are outside NIGMS mission and should be directed to the institutes covering those mission areas. ​​ Research on systemic biological responses to challenges spanning multiple organ systems, including the physiological consequences of circadian rhythms and stress, as related to human health.

This may include research on the physiology of integration of total body responses or interdisciplinary studies aimed at elucidating the complex interactions between circadian rhythms, metabolism, immune function, and physiological processes across multiple organ systems.

NOTE: Studies of pathophysiology of sleep and circadian rhythm disorders are outside the NIGMS mission, as are studies focusing on physiology of specific organs or organ systems within the missions of other institutes. Zuzana Justinova, M. D.

, Ph. D. Research on delivery systems and novel strategies designed to improve permeability, absorption, stability, bioavailability, biodistribution and pharmacokinetics of small molecules and biologics.

These can include antibodies, aptamers, extracellular vesicles, nanoparticle systems (e.g., lipid nanoparticles, solid lipid nanoparticles, liposomes, dendrimers, micelles, nanospheres, silica particles), nucleic acids, proteins and peptides, viruses, chemical cages, novel materials, polymeric particles and implants, and platforms/devices with an emphasis on drug targeting, release and pharmacokinetics.

May also include studies on understanding and manipulating the transport of therapeutic agents across biological barriers, routes of administration to improve drug delivery, engineering approaches to enhance drug and gene delivery, and development of next-generation drug delivery systems to improve the efficacy and specificity of treatments by leveraging advanced materials and nanotechnology.

NOTE: Studies aimed at efficacy for specific diseases (including but not limited to pre-clinical models), or those focused on obtaining regulatory approval, will not be accepted and should be discussed with the institutes focused on those missions. Small business (SBIR) and tech transfer (STTR) grants in pharmacological and clinical areas.

Basic and clinical studies focused on sepsis and septic shock, with an emphasis on the host response. This includes studies on unraveling the complex pathophysiology and heterogeneity of sepsis, identifying novel biomarkers for early diagnosis and patient stratification, and developing strategies for translating this knowledge into improved diagnostics and therapies for sepsis patients.

Preclinical studies relying on murine models of sepsis are unlikely to be supported by NIGMS; for more details on NIGMS priorities for sepsis research, please see NOT-GM-19-054 . Systemic Immune/Inflammatory Responses Research aimed at improving understanding the mechanisms governing innate immune responses and host-pathogen dynamics.

This includes studies elucidating the complex networks and pathways that underpin innate immunity and acute inflammation, with implications for developing novel therapeutic strategies against infectious diseases, inflammation, and immune dysregulation.

Examples of studies in this portfolio include cellular and molecular mediators of inflammation and immunity underlying complex body-wide pathophysiological responses, examination of the host defense mechanisms in model organisms (such as plants, C.

elegans, and fruit flies), in vitro studies of host defense using cutting-edge technologies, host defense mechanisms in the context of multi-organ interactions or evolution, and novel non-organ-specific host defense pathways.

NOTE: Studies focusing on the pathogenicity of microorganisms, antibiotic resistance, adaptive immunity or its mechanisms in allergic or autoimmune diseases, or of immune cells related to immune-related conditions will, in most cases, be more appropriate for NIAID.

For R35 (MIRA)-related questions, contact: For R01-related questions, contact: Basic mechanistic, translational, and clinical studies addressing physiology, biochemistry, and immunology of wound healing after injury (traumatic, burn, and surgical).

This includes: research directed toward an improved understanding of the fundamental processes underlying normal, excessive or impaired wound healing, tissue repair and regeneration; studies aimed at understanding phases and signaling pathways that regulate the wound healing process; and how dysregulation of these processes impacts injury-related wound healing.

Research focusing on healing of wounds associated with specific conditions (e.g., diabetic chronic wounds, keloids, fibrosis, mouth ulcers) should be directed to the appropriate categorical institute.

Biochemistry and Molecular Pharmacology Bioenergetics and Mitochondria Energy transducing enzymes of the mitochondrial inner and outer membranes, chloroplasts, and microorganisms; electron transport, photosynthesis, including biogenesis of cofactors and substrate transport.

Calcium Signaling and Compartmentalization Temporal and spatial signaling within cells, including calcium fluxes, diffusion, and pumps; regulation of signaling molecules by compartmentalization within organelles, and cellular sinks and releasing proteins.

Cell Surface Receptors, Ligands, and Interactions G protein-coupled receptors and cell surface receptors for drugs, endogenous ligands, and other stimuli; purpose is to understand basic biology and/or for validation as potential therapeutic targets.

Enzyme Mechanisms, Regulation, and Inhibition Individual enzyme mechanisms, regulation, modification, and inhibition to understand the catalytic specificity of synthesis, modification, or degradation of metabolites and macromolecules.

Intracellular Mediators of Signal Transduction Molecular pathways for signal transduction and regulation within cells, including second messengers such as kinases, phosphatases, adapter proteins, lipid messengers, phospholipases and others (excluding calcium). Includes intracellular nuclear and cytosolic receptors.

Pore-forming proteins specialized for ions (Na, K, Cl), ligand and voltage-gated, found at cell surface and organelle membranes. Includes ion channel blockers such as venoms and toxins. PIs with last names starting A-L, contact: PIs with last names starting with M-Z, contact: Zuzana Justinova, M.

D. , Ph. D.

Membrane Components and Cell-to-Cell Communications Scaffolding and functional components of cellular membranes and vesicles: structural lipids (e.g., cholesterol), integral proteins, and their modifications. Gap junctions and communications between cells. Metalloprotein Mechanisms Functions and mechanisms of metalloenzymes, including natural and synthetic macromolecules that form transition metal-utilizing proteins and transporters.

Pathways of Intermediary Metabolism and Catalysis Metabolic pathways and information flow; includes studies of transient intermediates and stable multi-enzyme complexes, and how catalytic processes and fluxes are affected by the intracellular milieu.

Redox Reactions and Oxidative Stress Pathways responsible for generation or decomposition of reactive species (O, N, S), and the modification of cellular constituents by oxidative stressors; chemistry and maintenance of cellular redox balance.

Trace Metal Transport and Homeostasis Regulation of trace metal ions (e.g., Fe, Co, Ni, Cu, Zn, As, Se, Mo, W), their transport, intracellular concentrations and speciation, and metal ion chaperones and ionopheres. Includes restriction of metal ion availability as a therapeutic intervention.

Chemistry and Chemical Biology Research focused on understanding and manipulating the roles of metal ions in biological processes by investigating their complex interactions with biological systems.

Approaches that leverage a multidisciplinary approach, combining cutting-edge techniques in synthetic chemistry, spectroscopy, and molecular biology to create and study novel metal complexes and their interactions with enzymes and other biological molecules essential to life. Technology development for basic biomedical research, including engineering tools and materials for applications at the molecular level.

Using chemical methods to produce tools to study or manipulate biology. Development of chemical tools, such as probes, polymers, and nanostructured assemblies for potential use in biological systems and medical applications. Chemical tools to study and manipulate protein signaling pathways and post-translational modifications.

Development of catalytic reactions, including transition metal catalysis, organocatalysis, photochemical and electrochemical reactions. Chemical Synthetic Methods Development of reagents and new synthetic methods. Includes theoretical studies of reaction mechanisms and computational approaches.

Design and Synthesis of Chemical Probes Design, synthesis, and testing of novel small molecule probes that target specific biological entities and pathways intended for the study of biological function. Includes development and approaches with docking libraries and screens.

Research aimed at an organ or organ system, or the pathophysiology or treatment of an identified disease, will in most cases be more appropriate for another institute. Design and synthesis of carbohydrate structures and their production through chemical synthesis or chemoenzymatic synthesis.

This includes the development of sophisticated glycochemical techniques (design and assembly of sugars and their analogs) that expand current methodologies for the synthesis, analysis, and utilization of complex carbohydrates, driving forward both fundamental science and translational research opportunities. Carbohydrate-containing macromolecules with an emphasis on carbohydrates and their binding partner(s).

Includes sugar transporters and carrier lipids, glycan processing enzymes, protein: glycan mediated interactions, and peptidoglycans. Natural Products Discovery and Analysis Identification and study of substances produced by living organisms that may form the foundation for therapeutic development. Analysis of organisms and their environments through the study of genetic information and biosynthetic pathways.

Includes molecules produced and altered in microbial communities. Studies focused on human microbiome metabolites and their associated disease pathogenesis may be more appropriate for other NIH Institutes or Centers.

Peptide Chemistry and Engineering Advancements in peptide research from the synthesis of novel scaffolds for enhanced stability and function to the use of peptides as chemical biology tools for studying enzyme functions and cellular processes. This also includes innovative methods in peptide synthesis, improved strategies for overcoming cellular barriers, and new therapeutic strategies.

Small business (SBIR) and tech transfer (STTR) grants in biochemical and biologically-relevant chemical areas. Includes new technology development. Engineering technologies to produce useful biological materials.

Uses biological methods to produce tools to study or manipulate biology. Mixture of physical and genetic engineering to create new biological entities and systems, or redesign of naturally occurring systems.

Research Capacity Building Institutional Development Award (IDeA) The IDeA program builds research capacity in states that historically have had low levels of NIH funding by supporting basic, clinical, and translational research, faculty development, and infrastructure improvements.

Health Research Programs for Federally-Recognized Tribes The Health Research Programs for Federally-recognized Tribes supports health-related research, research career enhancement, and research infrastructure enhancement activities at federally-recognized Tribes, Tribal colleges or universities, Tribal health programs, or Tribal organizations (collectively, Tribal entities).

Support for Research Excellence (SuRE) This program seeks to strengthen research capacity and provide research support to the faculty at institutions that receive limited NIH research support and furnish students with high-quality undergraduate and/or graduate experiences in biomedical sciences research.

Biomedical Research Environment & Sponsored Programs Administration Development (BRE-SPAD) This program aims to support resource-limited institutions to conduct research, enhance their research environments, and increase sponsored programs administration capacity. BRE-SPAD is designed to support the needs of organizations that are in different stages of biomedical research capacity building. NIGMSBRE-SPAD@nigms.

nih.

gov Training and Workforce Development Cross-Disciplinary Pathway Programs (CPP) Science Education Partnership Award (SEPA) The overarching goal of this NIH Science Education Partnership Award (SEPA) program is to support educational activities that increase understanding of biomedical research among pre-college (pre-kindergarten to grade 12) individuals, and to encourage awareness of and continued interest in careers in science, technology, engineering, and mathematics (STEM).

All requests for general information about SEPA awards should be directed to: Biomedical Undergraduate Research Training (BURT) Program (T34) The goal of the Institutional Biomedical Undergraduate Research Training (BURT) Program is to strengthen research training environments and develop a pool of well-trained students who complete their baccalaureate degrees in biomedically-related fields, and transition into and complete biomedical, research-focused higher degree programs (such as Ph.

D. or M. D.

/Ph. D.)

All requests for general information about BURT training grants should be directed to: Tribal Undergraduate to Graduate Research Training and Leadership Experiences (TURTLE) Program (UE5/T34) and (UE5/T32) The TURTLE program is for federally recognized American Indian/Alaska Native (AI/AN) Tribal Entities to develop a pool of scientists to support the development of individuals who have the skills required to conduct AI/AN health research in a culturally appropriate, ethically responsible and rigorous manner, to complete their degrees in a biomedical field, and to transition into careers in the biomedical research workforce.

All requests for general information about BURT training grants should be directed to: NIGMSTurtle@nigms. nih. gov Medical Scientist Training Program (MSTP, leading to combined clinical and research doctorate degrees) The MSTP supports the integrated dual degree training that leads to the award of both clinical (that is, M.

D. , D. O.

, D. V. M.

, D. D. S.

, Pharm. D. , etc.) and research doctorate degrees (Ph.

D.) that implements effective and evidence-informed approaches. With the dual qualification of rigorous scientific research and clinical practice, graduates will be equipped with the skills to develop research programs that accelerate the translation of research advances to the understanding, detection, treatment, and prevention of human disease, and to lead the advancement of biomedical research.

MSTP assures selected trainees a choice of a wide range of pertinent graduate programs in the biological, chemical, and physical sciences that, when combined with training in medicine, lead to a dual degree. Programs are encouraged to provide a breadth of doctoral research training opportunities consistent with individual institutional strengths.

In addition to the above disciplines, support of trainees in other disciplines such as computer sciences, social and behavioral sciences, economics, epidemiology, public health, bioengineering, biostatistics, and bioethics is encouraged.

Proposed MSTP programs should be flexible and adaptable in providing each trainee with the appropriate background in the sciences relevant to medicine yet be rigorous enough to enable graduates to function independently in both basic research and clinical investigation. Per NOT-GM-25-024 , NIGMS will consider applications from Institutions in an