Hutchinson-Gilford syndrome

This PA is a new initiative to support research to understand how mutations in the gene for lamin A/C affect nuclear structure, thus leading to bothdysfunction of the nuclear envelope, and depending on the mutation, Hutchinson-Gilford syndrome in humans (Eriksson et al., manuscript in preparation). Lamins A and C are coded by a single developmentally regulated gene designated LMNA; lamin C is a splice variant and lacks the carboxyl terminus present in lamin A. At least 6 other rare human disorders due to lamin A/C mutations (known collectively as laminopathies) besides HGS have been described so far: Emery-Dreifuss muscular dystrophy (Bonne et al., 1999), dilated cardiomyopathy (Fatkin et al., 1999), familial partial lipodystrophy (Shackleton et al., 2000), limb girdle

muscular dystrophy (Muchir et al., 2000), Charcot Marie-Tooth disorder type 2 (De Sandre-Giovanni et al., 2002), and mandibuloacral dysplasia (Novelli et al., 2002). These disorders and their relationship to LMNA mutations have been reviewed recently {Burke and Stewart (2002)}, and Hutchinson (2002) has reviewed the function of lamins in the nuclear envelope.

This PA will use the National Institutes of Health (NIH) research project grant R01 award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Contact the program staff listed under "inquiries" for further information. This PA uses just-in-time concepts. It also uses the modular as well as the non-modular budgeting formats (see http://grants.nih.gov/grants/funding/modular/ modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular format. Otherwise follow the instructions for non-modular research grant applications.

This program does not require cost sharing as defined in the current NIH Grants Policy statement at http://grants.nih.gov/ grants/policy/nihgs_2001/part_i_1.htm.

Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). The PHS 398 is available at http://grants.nih.gov/ grants/funding/phs398/phs398.html in an interactive format. For further assistance contact Grants Info, 301-435-0714, e-mail: GrantsInfo@nih.gov.

Applications submitted in response to this PA will be accepted at the standard application deadlines, which are available at http://grants.nih.gov/grants/dates.htm. Application deadlines are also indicated in the PHS 398 application kit.

Applications must be received by or mailed before the receipt dates described at http://grants.nih.gov/grants/funding/submissionschedule.htm. The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.

Contact: Felipe Sierra, Biology of Aging Program, National Institute of Aging, Gateway Building, Room 2C231, Bethesda, MD 20892-9525 USA, 301-496-6402, fax: 301-402-0010, e-mail: sierraf@nia.nih.gov; Dr. Stephen Goldman, Vascular Biology Research Program, Division of Heart and Vascular Disease, National Heart, Lung and Blood Institute, Bethesda, MD 20892-7956, USA, Carrier Zip 20814, 301-435-0560, fax: 301-480-2858, e-mail: goldmans@nhlbi. nih.gov. Reference: PA No. PA-03-069.

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