Letters of Intent

Some NIH funding opportunities suggest that you send a letter of intent before you apply. Learn on this page why the letter helps and what to include.

Additional Letters

Beyond Types of Letters for Grant Applications, you may need to include other letters with your NIH application or just-in-time before award.

Neutrophil Dysregulation in COVID-19

Analysis of Autoantibodies

Study of How COVID-19 Affects Blood Cells and the Immune System

A study about how SARS-CoV-2, the virus that causes COVID-19, affects the body, specifically how it affects blood cells and the immune system.

Contact Information

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Toll free: 1-800-411-1222
TTY: 1-866-411-1010
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Email: prpl@mail.cc.nih.gov

SARS-CoV-2 Genetics

Transatlantic Task Force on Antimicrobial Resistance (TATFAR)

TATFAR was created in 2009 to address the urgent threat of antimicrobial resistance (AMR). TATFAR’s technical experts from Canada, the European Union (EU), Norway, the United Kingdom, and the United States collaborate and share best practices to strengthen domestic and global efforts to combat AMR. 

The Centers for Disease Control and Prevention (CDC) currently serves as the secretariat for TATFAR, providing administrative support and maintaining the website for the taskforce. 

U.S. representatives to TATFAR include the U.S. Department of Health and Human Services (co-chair), NIH (NIAID), CDC, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the U.S. Department of Agriculture, the U.S. Department of Defense, and the Environmental Protection Agency.  

Read more about this network: TATFAR

Main Areas of Focus

TATFAR’s goal is to improve cooperation between the United States and EU in four key areas:

  1. Appropriate antimicrobial use in human and veterinary medicine.
  2. Surveillance and prevention of AMR.
  3. Strategies to improve financial incentives, access, research, and development of antimicrobial drugs, diagnostics and alternatives.
  4. Cross-cutting actions to improve awareness and disseminate information from TATFAR.
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Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X)

The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) global partnership was created to help address the threat of antibiotic resistance. 

CARB-X is funded by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the United States Department of Health and Human Services; the Wellcome Trust in the United Kingdom; Germany’s Federal Ministry of Education and Research (BMBF); the United Kingdom Government’s Department of Health and Social Care (DHSC), through its Global Antimicrobial Resistance Innovation Fund (GAMRIF); the Bill & Melinda Gates Foundation; and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). For more information, please see Funding Partners.

Read more about this network: CARB-X

Major Areas of Focus

CARB-X is focused on the preclinical discovery and development and Phase 1 clinical trials of new antibacterial products (including therapeutics, vaccines, and diagnostics) to help address the threat of antibiotic resistance.

Over the last several decades there has been a continual withdrawal of pharmaceutical companies engaged in developing new antibiotics. In 1990, there were at least 18 large pharmaceutical companies actively developing antibiotics. As of April 2020, there are 4. 

CARB-X provides funding for companies with innovative and promising solutions to antibiotic resistance. CARB-X also provides the business support and drug development expertise to that companies, including start-ups, need to increase their odds of success. NIAID provides technical support and preclinical drug development services to CARB-X awardees.

Contact Information

Anita Sheoran, Ph.D., Office of Biodefense, Research Resources and Translational Research

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Microbiome Immunity

*This project is not currently being actively pursued.

Project Title: The role of the anti-commensal antibody repertoire in the differential outcomes of symptomatic versus asymptomatic infection in SARS-CoV-2

NIAID Principal Investigator: Yasmine Belkaid, Ph.D.
Former Chief, Metaorganism Immunity Section (LISB)

Tais B. Saito, D.V.M., M.S., Ph.D.

Chief, Vector-Pathogen-Host Interaction Unit
NIH Distinguished Scholar

Major Areas of Research

  • Host immune components in establishment of vector borne infection and disease pathogenesis
  • Role of epidermal/dermal cells in vector transmission-associated inflammation
  • Dynamics of cutaneous immunoregulation during tick attachment and pathogen transmission
  • Role of vector transmission in development of pathogen specific immunity
  • Identification of determinants of disease severity in ehrlichial and rickettsial infection and their potential as immunotherapy
  • Identification of tick and bacterial factors associated with establishment of infection and bacterial persistence
     

Biography

Dr. Saito received a D.V.M. from the State University of Londrina, Parana, Brazil. She completed a residency in clinical practice and small animal surgery as well as a Master of Science degree at the same University.  Dr. Saito then earned her Ph.D. in veterinary medicine and infectious diseases at the State University of Sao Paulo, Brazil. In 2009, she moved to the U.S. to conduct postdoctoral research at the University of Texas Medical Branch at Galveston (UTMB). Later she was appointed as an Instructor at UTMB and as a Research Assistant Professor in 2017.  Dr. Saito was recruited to the DIR NIAID in 2020 as a tenure-track investigator and is currently Chief of the Vector-Pathogen-Host Interaction Unit in the Laboratory of Bacteriology.   She serves as a review editor for Frontiers in Cellular and Infection Microbiology and as ad hoc reviewer for numerous journals in her field.  She is an advocate for diversity in the biomedical sciences.

Program Description

Environmental changes are driving a global increase in arthropod borne infections that, in many cases, cause severe life-threatening illnesses. An example in the United States is human ehrlichioses, an emerging infectious disease caused by Ehrlichia spp. An increase in tick borne infections and recognition of new pathogen species in recent years emphasize the importance of understanding the disease initiation and determinants of susceptibility. In 2009, a new species of Ehrlichia was detected in human patients in United States, Ehrlichia muris eauclairensis, transmitted by the tick vector Ixodes scapularis. These blood-feeding arthropods use their salivary proteins to manipulate the host local immune reaction at the bite site, facilitating prolonged attachment. Many pathogens, before and during transmission, are known to modulate the tick tissue environment, as well as their own transcriptome/proteome. Therefore, the induction of infection in the skin involves an extremely complex interaction of modulatory factors from the tick, pathogen and the host immune response.

Our research group is interested in understanding the immune signaling involved in vector transmission of pathogens, primarily focusing on tissue-specific innate host responses induced by ehrlichial (and rickettsial) diseases. We believe that this initial response, at the skin site of the tick-pathogen interaction with the host, is associated with disease development and progression to severe outcome.

Our animal model of ehrlichiosis, using the natural mode of infection by tick transmission, results in increased bacterial replication and dissemination throughout the body and more severe outcome, compared to intradermal needle injection of ehrlichiae (Saito and Walker, 2015). The dermal reaction to tick inoculation of the ehrlichial pathogen demonstrates intense inflammatory infiltration and a strong IL-1 cytokine family signature. At the tick attachment site we observe intense tissue damage, with massive infiltration of granulocytes. The most impressive inflammatory infiltration is observed during the peak of tick feeding and after spontaneous detachment; however, we observed a dynamic response of the recruiting innate cells. Moreover, intradermal needle inoculation of bacteria did not induce extensive skin inflammation nor severe disease outcome. Similarly to other rickettsial infections, we identified a persistence of ehrlichial antigen at the skin of infected animals. These findings demonstrate induction of an inflammatory response, potentially associated with successful bacterial replication and disease pathogenesis.

Our ultimate goal is to better understand this complex vector-host-pathogen interaction at the cutaneous interface and its influence in immunopathogenesis of disease severity and/or development of protective immunity. By improving our knowledge of skin immune response to tick borne infections, we will be able to further evaluate the involvement of the initial immune-mediators on the development of dermal protective immunity to arthropod-transmitted diseases.

Selected Publications

Liu Y, Zhou C, Su Z, Chang Q, Qiu Y, Bei J, Gaitas A, Xiao J, Drelich A, Khanipov K, Jin Y, Golovko G, Saito TB, Gong B. Endothelial Exosome Plays a Functional Role during Rickettsial Infection. mBio. 2021 May 11;12(3):e00769-21. 

Saito TB, Bechelli J, Smalley C, Karim S, Walker DH. Vector Tick Transmission Model of Spotted Fever Rickettsiosis. Am J Pathol. 2019 Jan;189(1):115-123. 

Smalley C, Bechelli J, Rockx-Brouwer D, Saito T, Azar SR, Ismail N, Walker DH, Fang R. Rickettsia australis Activates Inflammasome in Human and Murine Macrophages. PLoS One. 2016 Jun 30;11(6):e0157231. 

Saito TB, Walker DH. A Tick Vector Transmission Model of Monocytotropic Ehrlichiosis. J Infect Dis. 2015 Sep 15;212(6):968-77. 

Saito TB, Thirumalapura NR, Shelite TR, Rockx-Brouwer D, Popov VL, Walker DH. An animal model of a newly emerging human ehrlichiosis. J Infect Dis. 2015 Feb 1;211(3):452-61. 

Shelite TR, Saito TB, Mendell NL, Gong B, Xu G, Soong L, Valbuena G, Bouyer DH, Walker DH. Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected]. PLoS Negl Trop Dis. 2014 Jul 10;8(7):e2966. 

Visit PubMed for a complete publication list.

Section or Unit Name
Vector-Pathogen-Host Interaction Unit
Lab/Program Name
First Name
Tais
Last Name
Saito
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D.V.M., M.S., Ph.D.
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Program Description

Environmental changes are driving a global increase in arthropod borne infections that, in many cases, cause severe life-threatening illnesses. An example in the United States is human ehrlichioses, an emerging infectious disease caused by Ehrlichia spp. An increase in tick borne infections and recognition of new pathogen species in recent years emphasize the importance of understanding the disease initiation and determinants of susceptibility. In 2009, a new species of Ehrlichia was detected in human patients in United States, Ehrlichia muris eauclairensis, transmitted by the tick vector Ixodes scapularis. These blood-feeding arthropods use their salivary proteins to manipulate the host local immune reaction at the bite site, facilitating prolonged attachment. Many pathogens, before and during transmission, are known to modulate the tick tissue environment, as well as their own transcriptome/proteome. Therefore, the induction of infection in the skin involves an extremely complex interaction of modulatory factors from the tick, pathogen and the host immune response.

Our research group is interested in understanding the immune signaling involved in vector transmission of pathogens, primarily focusing on tissue-specific innate host responses induced by ehrlichial (and rickettsial) diseases. We believe that this initial response, at the skin site of the tick-pathogen interaction with the host, is associated with disease development and progression to severe outcome.

Our animal model of ehrlichiosis, using the natural mode of infection by tick transmission, results in increased bacterial replication and dissemination throughout the body and more severe outcome, compared to intradermal needle injection of ehrlichiae (Saito and Walker, 2015). The dermal reaction to tick inoculation of the ehrlichial pathogen demonstrates intense inflammatory infiltration and a strong IL-1 cytokine family signature. At the tick attachment site we observe intense tissue damage, with massive infiltration of granulocytes. The most impressive inflammatory infiltration is observed during the peak of tick feeding and after spontaneous detachment; however, we observed a dynamic response of the recruiting innate cells. Moreover, intradermal needle inoculation of bacteria did not induce extensive skin inflammation nor severe disease outcome. Similarly to other rickettsial infections, we identified a persistence of ehrlichial antigen at the skin of infected animals. These findings demonstrate induction of an inflammatory response, potentially associated with successful bacterial replication and disease pathogenesis.

Our ultimate goal is to better understand this complex vector-host-pathogen interaction at the cutaneous interface and its influence in immunopathogenesis of disease severity and/or development of protective immunity. By improving our knowledge of skin immune response to tick borne infections, we will be able to further evaluate the involvement of the initial immune-mediators on the development of dermal protective immunity to arthropod-transmitted diseases.
 

Selected Publications

Liu Y, Zhou C, Su Z, Chang Q, Qiu Y, Bei J, Gaitas A, Xiao J, Drelich A, Khanipov K, Jin Y, Golovko G, Saito TB, Gong B. Endothelial Exosome Plays a Functional Role during Rickettsial Infection. mBio. 2021 May 11;12(3):e00769-21. 

Saito TB, Bechelli J, Smalley C, Karim S, Walker DH. Vector Tick Transmission Model of Spotted Fever Rickettsiosis. Am J Pathol. 2019 Jan;189(1):115-123. 

Smalley C, Bechelli J, Rockx-Brouwer D, Saito T, Azar SR, Ismail N, Walker DH, Fang R. Rickettsia australis Activates Inflammasome in Human and Murine Macrophages. PLoS One. 2016 Jun 30;11(6):e0157231. 

Saito TB, Walker DH. A Tick Vector Transmission Model of Monocytotropic Ehrlichiosis. J Infect Dis. 2015 Sep 15;212(6):968-77. 

Saito TB, Thirumalapura NR, Shelite TR, Rockx-Brouwer D, Popov VL, Walker DH. An animal model of a newly emerging human ehrlichiosis. J Infect Dis. 2015 Feb 1;211(3):452-61. 

Shelite TR, Saito TB, Mendell NL, Gong B, Xu G, Soong L, Valbuena G, Bouyer DH, Walker DH. Hematogenously disseminated Orientia tsutsugamushi-infected murine model of scrub typhus [corrected]. PLoS Negl Trop Dis. 2014 Jul 10;8(7):e2966.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Host immune components in establishment of vector borne infection and disease pathogenesis
  • Role of epidermal/dermal cells in vector transmission-associated inflammation
  • Dynamics of cutaneous immunoregulation during tick attachment and pathogen transmission
  • Role of vector transmission in development of pathogen specific immunity
  • Identification of determinants of disease severity in ehrlichial and rickettsial infection and their potential as immunotherapy
  • Identification of tick and bacterial factors associated with establishment of infection and bacterial persistence