MicroRNA-31 regulates neutrophil migration and activation

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Tyler  Pikes
Organization: PURDUE UNIVERSITY
Fiscal Year: 2024
Award: $48,974
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY
Neutrophils are white blood cells involved in the innate immune response. They are the
most abundant white blood cell in circulation and are involved in fighting infections as well
as initiating inflammatory immune responses and contribute to certain autoimmune
diseases. Therefore, regulation of neutrophil activity is crucial in maintaining homeostasis
in the immune system. Yet the specific mechanisms or which molecules are involved in
regulating neutrophil functions are still not fully understood. Previous studies in our lab
discovered microRNA-31 (miR-31) neutrophil motility in zebrafish. In this study we
propose to validate the function of miR-31 in human and uncover the underlying molecular
mechanism. We propose to discover key target genes of miR-31 that are important in
regulating neutrophil migration. Through a small-scale genetic screen using the
neutrophil-specific CRISPR/Cas9-based gene inactivation technique, I identified a
specific target gene of miR-31, efnb2b, involved in regulating neutrophil motility. Efnb2b
is a ligand for Eph receptors important for heart morphogenesis and angiogenesis via
regulation of cell adhesion and cell migration but not characterized in the immune system.
We propose to understand the signaling pathway regulated by efnb2 in neutrophils.
Completion of the proposed study will advance our understanding of neutrophils and
innate immunity, leading to possible therapeutic developments for neutrophil-related
diseases.

Terms: <1-Phosphatidylinositol 3-Kinase><Actins><Active Oxygen><Affect><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Arthritis><Assay><Asthma><Autoimmune Diseases><Autoregulation><Bioassay><Biological><Biological Assay><Biological Function><Biological Process><Biotin><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Blood leukocyte><Body Tissues><Brachydanio rerio><Bronchial Asthma><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Calcium><Cancers><Carbol><Carbolic Acid><Cas nuclease technology><Cell Adhesion><Cell Body><Cell Locomotion><Cell Migration><Cell Movement><Cell Nucleus><Cells><Cellular Adhesion><Cellular Migration><Cellular Motility><Chemoattractants><Chemotactic Factors><Chemotaxins><Chemotaxis><Circulation><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Clutch Size><Complex><Cytoplasmic Granules><DNA Therapy><Danio rerio><Data><Defect><Disease><Disorder><Eph Receptor Ligands><Ephrins><Gene Down-Regulation><Gene Inactivation><Gene Silencing><Gene Targeting><Gene Transcription><Gene Transfer Clinical><Genes><Genetic Alteration><Genetic Change><Genetic Intervention><Genetic Screening><Genetic Transcription><Genetic defect><Heart><Homeostasis><Human><Hydroxybenzene><Image><Immune response><Immune system><Immunological response><Infarction><Infection><Inflammation><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Inflammatory Response><Innate Immune Response><Innate Immune System><Innate Immunity><Knock-out><Knockout><Knowledge><Label><Larva><Leukocytes><Leukocytes Reticuloendothelial System><Ligase><Ligase Gene><Lipids><Luciferase Immunologic><Luciferases><Malignant Neoplasms><Malignant Tumor><Marrow Neutrophil><Marrow leukocyte><Mediating><Messenger RNA><Methods><Micro RNA><MicroRNAs><Modern Man><Molecular><Morphogenesis><Motility><Mutation><Native Immunity><Natural Immunity><Neutrophil Activation><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Granulocyte><Neutrophilic Infiltrate><Neutrophilic Leukocyte><Non-Specific Immunity><Nonspecific Immunity><Nucleus><Oxidative Burst><Oxygen Radicals><PI-3 Kinase><PI3-Kinase><PI3CG><PI3KGamma><PI3k><PIK3><PIK3CG><PIK3CG gene><Pathology><Phagocytosis><Phenols><Phenotype><Phosphatidylinositol 3-Kinase><Phosphatidylinositol-3-OH Kinase><Phosphoinositide 3-Hydroxykinase><Physiological Homeostasis><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Pro-Oxidants><Process><Proteins><PtdIns 3-Kinase><RNA Expression><Reactive Oxygen Species><Regulation><Reporter><Reporting><Respiratory Burst><Role><Signal Pathway><Small RNA><Synthetases><Techniques><Time><Tissues><Transcript><Transcription><Transcription Repression><Transcriptional Repression><Type I Phosphatidylinositol Kinase><Type III Phosphoinositide 3-Kinase><Vitamin H><White Blood Cells><White Cell><Wound Repair><Zebra Danio><Zebra Fish><Zebrafish><angiogenesis><arthritic><autoimmune condition><autoimmune disorder><autoimmunity disease><biologic><cell motility><chronic inflammatory disease><coenzyme R><complement chemotactic factor><cytokine><discover genes><fighting><gene discovery><gene function><gene repair therapy><gene repression><gene therapy><gene-based therapy><gene-based treatment><gene-directed therapy><gene-targeted therapy><gene-targeted treatment><genetic therapy><genome mutation><genomic therapy><granule><host response><imaging><immune system response><immunoresponse><in vivo><infarct><inflammatory disease of the intestine><inflammatory disorder of the intestine><innovate><innovation><innovative><intestinal autoinflammation><leukocyte oxidative burst><mRNA><malignancy><miRNA><miRNAs><migration><morphogenetic process><mouse model><murine model><neoplasm/cancer><neutrophil><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><overexpress><overexpression><pathogen><recruit><repair><repaired><response><social role><therapeutic agent development><therapeutic development><tissue wound><transcriptional silencing><white blood cell><white blood corpuscle><wound><wound healing><wound recovery><wound resolution><wounding><wounds>