This grant application proposes to expand and extend the services of the Massachusetts General Hospital Microarray Facility to investigators within the greater Boston community who are supported by grants awarded by the National Heart Lung Blood Institute. Although microarray analysis has opened up the potential to explore the interactions of large numbers of genes simultaneously, the obstacles to successful execution of this work are substantial. One of the chief hurdles to microarray analysis has been cost. Given the imperative to repeat assays in order to ensure reproducibility, this cost has made it difficult, if not impossible, for the typical academic lab to afford to conduct complex microarray studies. By using oligonucleotides synthesized by the MGH Oligonucleotide Facility and arraying our own oligos, we expect to lower substantially this cost barrier. Other factors that have impeded progress in microarray work have included problems with clone/gene availability and/or contamination when using spotted cDNAs, lack of probe or array reproducibility, and insufficient access to bioinformatics expertise in the analysis of very large data sets. Through our commitment to the use of spotted oligonucleotides as the probe sequences on microarrays, the issue of clone availability and contamination should be resolved. Bioinformatics as well as biological solutions to the problem of array reproducibility have been addressed in this grant application. Finally, with the recruitment of several leading local biostatisticians and bioinformaticians as co-investigators or consultants, the MGH Microarray Facility has assembled the requisite expertise and effort to facilitate a collaborating investigator's ability to analyze the large data sets generated by microarray techniques. The resources of this grant will be devoted to supporting the extensive community of NHLBI funded investigators at the major teaching hospitals and universities in the Boston area, including many younger investigators who have not previously had access to this important but costly research tool.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL072358-01
Application #
6571610
Study Section
Special Emphasis Panel (ZHL1-CSR-D (S1))
Program Officer
Ye, Jane
Project Start
2002-09-30
Project End
2006-07-31
Budget Start
2002-09-30
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$743,061
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Fitzgerald, Michael L; Xavier, Ramnik; Haley, Kathleen J et al. (2007) ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. J Lipid Res 48:621-32
Kuo, Winston Patrick; Liu, Fang; Trimarchi, Jeff et al. (2006) A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies. Nat Biotechnol 24:832-40
Jaffe, Iris Z; Mendelsohn, Michael E (2005) Angiotensin II and aldosterone regulate gene transcription via functional mineralocortocoid receptors in human coronary artery smooth muscle cells. Circ Res 96:643-50
Kim, Woojin Scott; Fitzgerald, Michael L; Kang, Kihwa et al. (2005) Abca7 null mice retain normal macrophage phosphatidylcholine and cholesterol efflux activity despite alterations in adipose mass and serum cholesterol levels. J Biol Chem 280:3989-95
Okuhira, Kei-ichiro; Fitzgerald, Michael L; Sarracino, David A et al. (2005) Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux. J Biol Chem 280:39653-64
Lee, Mei-Ling Ting; Whitmore, G A; Bjorkbacka, Harry et al. (2005) Nonparametric methods for microarray data based on exchangeability and borrowed power. J Biopharm Stat 15:783-97
Fitzgerald, Michael L; Okuhira, Kei-Ichiro; Short 3rd, Glenn F et al. (2004) ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities. J Biol Chem 279:48477-85