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ARRA Investments in Genetics Related to the Immune System and Infectious Disease

Public Health Burden
The basic science of genetics seeks to understand biological organisms and processes at the DNA level focusing on gene function, variation and expression. Since the expression of genes is essential to all biological processes, it is no surprise that the underlying cause of nearly all diseases have a genetic basis. Accordingly, conducting research genetic determinants of diseases not only aids in understanding the causes and factors of disease but will assist in finding disease treatments and detection methods.

Gene Function and Pathway Discovery
One of the most beneficial aspects of genetic studies is the capability to elucidate the function of the gene’s product (protein) and to understand the role of gene product(s) in a multi-component pathway or process. ARRA funds were awarded for projects aimed at:
  • Identifying the role of genetic factors on inflammatory pathways that prevent immune system recovery in HIV-infected patients, which may lead to interventions to help improve immune system recovery.1
  • Understanding the processes that lead to genetic variations in the major malaria parasite Plasmodium falciparum which could aid in developing malaria vaccines and novel therapies.2
  • Providing insight into how two proteins, CcrQ and Notchi, contribute to immunodeficiency and transformation to inform the development of therapies against immune-mediated disease.3
Functional Genomics and Systems Biology
Technological advances in molecular biology have facilitated the ability to study the coordinated role of subsets of genes within an organism’s genome in complex biological processes. This capability has greatly increased the understanding of comprehensive effects of diseases, treatments and disorders in biological organisms/systems. ARRA grants support research efforts in this field including:
  • A project aimed at determining the gene expression profile associated with the development of chronic graft rejection to better understand the contribution of the immune response, differential gene expression and genetic variability to the development of chronic renal allograft rejection.4
  • A study that proposes a comprehensive framework for identifying the network of genes involved in bacterial antibiotic resistance. If successful, the results will lead to new methods for combating antibiotic resistance.5
  • Another project aims to identify small genetic host variations that can influence the outcome of hepatitis C virus infection by studying the human proteome, the entire complement of proteins coded for in the human genome.6
  • A project intended to develop technologies for gene expression profiling, proteomics, and complex trait genetics to advance the understanding of kidney transplantation.7
Gene Therapy
Gene therapy involves the introduction of functional genes or other genetic elements that correct for diseases or conditions caused by defective genes within the recipient (i.e. human patient). Many NIAID-supported gene therapy studies were funded by ARRA grants including:
  • A pre-clinical research study that tests new strategies for improving the efficacy and durability of retroviral gene therapy to minimize potential side effects.8
  • Investigation of whether RNA interference, which can block the expression of genes, can be used as a potential therapy for HIV by protecting cells from viral infection.9
  • Efforts to provide new ribozymes, catalytic RNA molecules, and other inhibitory RNAs for inhibition of HIV-1 infection and to identify the best ribozyme-HIV target strategies for future gene therapy.10
  • A study aimed at improving the safety and efficacy of adenovirus vectors which will aid in the development of gene therapy for tumors.11
Genetic Screening, Monitoring and Diagnostics
Detection of variations in the DNA sequence of genes allows for the identification of potential diseases, disorders or susceptibilities to medical conditions in individuals. The ability to predictively identify these conditions will lead to preventative and more effective therapies. Examples of ARRA funded projects in this field of genetics include:
  • Research aimed at understanding the mechanisms underlying development of allergic disease and to uncover genes for the identification of children at higher risk for severe asthma.12
  • Investigations in determining the relative importance of genetics and sex hormonal exposure as the driving forces for autoimmune disease development which may significantly aid in screening and treating young girls and women with a predisposition for these diseases.13
  • A study of whether genetic variants are, in part, responsible for the differing outcomes of transplant recipients treated with similar immunosuppressive therapy which could lead to the ability to individualize therapy based on genetics to improve long-term patient and graft survival.14
  • Research designed to better understand the immune responses to the sexually transmitted disease Chlamydia in order to predict the outcome of infectious diseases based on the host’s genetic information. 15

  1. 1R21AI078774-01A2 -- Innate Immune Response Genetics and T cell Activation in Treated HIV Infection -- Hunt, Peter W (CA)
  2. 1R56AI068052-01A3 -- Plasmodium Recombination of Machinery -- Kumar, Nirbhay (MD)
  3. 1R01AI079213-01 -- Mechanisms of Lymphocyte Gene Regulation by E2A and Notch1 -- Kee, Barbara Lynne (IL)
  4. 3U01AI070107-04S1 -- Genomics of Chronic Renal Allograft Rejection -- Murphy, Barbara T (NY)
  5. 1R56AI077562-01A1 -- Comprehensive Genetic Characterization of Antibiotic Resistance -- Tavazoie, Saeed F (NJ)
  6. 1R21AI075015-01A1 -- Proteome-wide Identification of RNA-binding Proteins -- Kao, Cheng C (IN)
  7. 3U19AI063603-05S1 -- Genomics for Kidney Transplantation -- Salomon, Daniel Rene (CA)
  8. 2R01AI043745-11A2 -- Gene Therapy for Canine X-linked SCID -- Felsburg, Peter J (PA)
  9. 2R01AI055281-06A2 Modeling HIV-1 SiRNA Therapy -- Chen, Irvin (CA)
  10. 3R37AI029329-21S1 -- Enhancing the Intracellular Functioning of anti-HIV RNAs -- Rossi, John Joseph (CA)
  11. 1R21AI072774-01A2 -- Adenovirus Interaction with Platelets -- Lieber, Andre Michael (WA)
  12. 3U19AI070235-03S1 -- Epithelial Genes In Allergic Inflammation -- Khurana Hershey, Gurit K (OH)
  13. 1R21AI083804-01 -- The Relative Roles of Sex and Genes During Development of Systemic Autoimmunity -- Jorgensen, Trine Norgaard (OH)
  14. 3U19AI070119-04S1 -- Genomics of Kidney Transplantation -- Matas, Arthur J (MN)
  15. 1R21AI081050-01A1 -- System Genetics of Immune Pathways Induced by Chlamydia -- Miyairi, Isao (TN)

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Page Last Updated on June 30, 2018 NIH...Turning Discovery Into Health®