REQUIRED FORMAT FOR LETTERS OF INTENT, MICHELSON GRANTS THE FOUNDATION WILL DECLINE LOIs THAT DO NOT COMPLY WITH THIS FORMAT THIS IS A SAMPLE LOI FOR A FICTIONAL PROPOSAL Use Professional Letterhead with Your Complete Mailing Address, Email & Phone Number USE ¾ MARGINS; ARIAL/HELVETICA FONT 11; DO NOT EXCEED TWO PAGES Date Program Manager Michelson Grants in Reproductive Biology Found Animals Foundation Post Office Box 66370 Los Angeles CA 90066 Dear Sir or Madam, This is a Letter of Intent, seeking funding for a proposal entitled: “Destruction of Hypophyseal GnRH Receptors Using Intravenous Kryptonite: Proof of Concept Study in Mice” from the Found Animals Foundation. This is anticipated to be a three-year study, conducted in our laboratory and at the animal care facilities of our collaborator, Dr. Jane Doe, at the University of ABCDE. Proposed approach for developing a single dose non-surgical sterilant: We propose to conjugate kryptonite to a carrier peptide identified by phage planning that will be linked to gonadotropin releasing hormone (GnRH). When administered intravenously, the conjugate will home to the anterior pituitary and selectively bind to, and ablate the gonadotrophs, leading to permanent sterility. As GnRH is evolutionarily conserved in both male and female mammals, this treatment, if effective in mice, is hypothesized to be a candidate for a “universal sterilant” in the Foundation’s target species. Following proof of concept in mice we plan to submit a later proposal to test the product in male and female dogs and cats. The rationale for proposing this approach: In work published from our laboratory (Doe J: J Irreprod Res, 33:12-26, 2007) we showed that kryptonite can be administered intravenously and is selectively toxic to pituitary basophils via inhibition of the glutathione-methyl-peroxidase pathway. We are aware that cells expressing GnRH receptors are present in other body tissues, and that the proposed treatment has the potential of harming non-target cells; however, since non-target cells express the receptor at concentrations and binding affinities more than 1000X lower than in the pituitary, we hypothesize that this treatment will not be harmful to nontarget tissues. Simpson and colleagues (J Irreprod Res, 27:55-61, 2001) have demonstrated successful use of kryptonite linked to a carrier peptide and corticotropin releasing hormone in chemically ablating ACTH-secreting pituitary adenomas in the dog. An overview of required research (budget estimates not required): We propose a three-year study with general objectives of (i) identification and concentration of appropriate homing peptides from the murine hypophysis, using phage panning, (ii) chemical construction of the kryptonite/peptide/GnRH conjugate using techniques in use in our laboratory, (iii) dose titration of the conjugate in mice, first using an in vitro cell line expressing the GnRH receptor, and (iv) intravenous administration of the optimal dose, 2X dose and control dose of the conjugate to postpuberal mice, with subsequent safety/efficacy monitoring in a lifetime (18 month) study. Work on this project could be initiated in our laboratory on receipt of funding. 1 The investigators confirm that we have reviewed the required resources prior to submission of this letter of intent. Sincerely, Principal Investigator, PhD [email protected] EMAIL ADDRESSES REQUIRED HERE Co-Investigator, PhD (if applicable) [email protected] LOIs must be sent as an attachment to an email to [email protected]. In order to be considered for the Michelson Grants in Reproductive Biology, the project must pursue a technology, mechanism, or pathway representing an innovative approach to nonsurgical sterilization. Proposed research is not required to generate results that meet all of the Michelson Prize criteria in order to be funded; however, strong preference will be given to projects with the potential to produce a prize-winning product or technology, and approaches must represent a significant improvement over existing products. The Michelson Prize criteria are as follows: • • • • • • Single dose, permanent, non-surgical sterilant Safe and effective in male and female cats and dogs Ablates sex steroids and/or their effects Suitable for administration in a field setting Viable pathway to regulatory approval Reasonable manufacturing process and cost If the LOI is approved, investigators will be invited to submit a full grant application and will be sent grant proposal guidelines. Please do not submit a full proposal unless invited by Found Animals Foundation. TIPS FOR SUCCESS DO: • • • • • • Review the Canine and Feline Reproductive Resources, the Policy for Animals Involved in Research, and the Quality Research Practices Self-Assessment Checklist prior to submission and state in your letter of intent that you have completed this review. Keep in mind the mission of the MPG Program, which is to reduce shelter euthanasia of pets with a single-dose, permanent, safe sterilant. An injectable or implantable route of administration is preferred to oral, intranasal, or other formulations. LOIs pursuing bait or feed products will not be considered. Consider proposing a small pilot/proof of concept study rather than a large project based on an unproven concept. Follow all formatting requirements as shown in letter above. Use a title for your proposal that describes your work [i.e. NOT: “A Nonsurgical Sterilant for Dogs and Cats; BUT: “Destruction of Hypophyseal GnRH Receptors Using Intravenous Kryptonite: Proof of Concept Study in Mice”] DON’T: • Cite information on the pet overpopulation problem in your letter; the Foundation is already aware of the magnitude of this problem. • Propose a research direction that has already been done. 2