MASSACHUSETTS GENERAL HOSPITAL, THE
Each cell independently interprets extracellular signals to decide its fate. An outstanding question in developmental biology is how these decisions are coordinated across the developing tissue primordium to produce a functional organ of appropriate size. Extracellular signals called morphogens are a critical mechanism to regulate cell fates across an entire primordium, and multiple morphogen signals are coordinated during development and in adult tissue self- renewal. The research proposed here will address interactions between morphogens in the transforming growth factor beta (TGFB) family and those that stimulate the receptor tyrosine kinase (RTK) pathway. We will use genetic methods to investigate interactions in whole tissues, while the tissue grows or reorganizes. The model genetic organism Drosophila is used, because of the low level of genetic redundancy and the powerful tools available for in vivo experiments. Within a cell, TGF2 signals are interpreted by Smad signal transduction pathways. We primarily focus on one class of TGFB signals, the bone morphogenetic proteins (BMPs). Different levels of extracellular BMP activity stimulate different levels of nuclear Smads, thus determining the genes that are expressed. In addition, protein kinases stimulated by RTK signals can modulate the levels of nuclear Smads, which may alter the way that cells respond to BMP signals. Preliminary data suggest that RTK signals down-regulate the BMP- specific fly Smad Mad and the general fly Smad Medea. Aims 1 and 2 test the importance of this regulation during tissue growth and migration. Aim 3 will screen for new mechanisms that regulate BMP pathway activity upstream of Smads. The molecular components of these pathways are strongly conserved between flies and humans, so we anticipate that new mechanisms will be conserved as well. Thus, this work will be important to understand the underlying mechanisms associated with TGF2 dysfunction in human fibrosis, tumorigenesis, and vascular function. PUBLIC HEALTH RELEVANCE: Protein signals move between cells to coordinate decisions. We study how these signals make cells do the right thing at the right time.
| AWARD OVERVIEW |
| Award Number |
3R01GM060501-10A1S1 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$99,994 |
Project Location - City |
Boston |
| Award Date |
09/18/2009 |
Project Location - State |
MA |
| Project Status |
Completed |
Project Location - Zip |
02114-0000
|
| Jobs Reported |
0.00 |
Congressional District |
09 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
MASSACHUSETTS GENERAL HOSPITAL, THE |
| Recipient DUNS Number |
073130411
|
| Recipient Address |
55 FRUIT ST |
| Recipient City |
BOSTON |
| Recipient State |
Massachusetts |
| Recipient Zip |
02114-2621 |
| Recipient Congressional District |
09 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
TGF-beta family regulation of epithelial morphogenesis |
| Project Status |
Completed |
| Final Project Report Submitted |
Yes |
| Project Activities Description |
General Medical and Surgical Hospitals |
| Quarterly Activities/Project Description |
Since April 1, we have begun using our new Nikon Eclipse system for all our routine immunofluorescence microscopy. This has save enormous amounts of time, because the sensitivity of the microscope permits efficient assessment of the success of an experiment that is intended for confocal immunofluorescence analysis. With this preliminary assessement, we can effectively prioritize our use of the expensive and limited time on confocal microscopes. This is resulting in both cost and time savings for the laboratory.
In addition, the effect on morale among the laboratory personnel is quite noticeable, because they can obtain preliminary data independent of the availability of confocal microscopes. This is important, because I am currently training three new lab members, and the immediate feedback on their progress in learning techniques is invaluable.
We are now poised to carry out the critical immunofluorescence experiments of Aim 1 of the parent R01 grant. We have initiated immunofluorescence analyses for Aim 2, and preliminary tests indicate that this microscope is everything we had hoped for. We have purchased a 10X objective and a filter set for Cy5 wavelengths, to expand its utility.
As part of our work for Aim 2 of the parent grant, we entered into a collaboration with the laboratory of Dr. Michael O'Connor (HHMI, Univ. of Minn.) to examine the requirement of the Drosophila Activin-like signaling system in Drosophila oogenesis. We tested this hypothesis that defects in eggshell formation were due to early problems in the developmentally regulated endocycles that create the polyploid somatic cells that secrete the eggshell. All our data were collected with this Nikon Eclipse microscope system. We found conclusive evidence for reduced DNA synthesis and subsequent failure of egg chamber development. This work is now being prepared for publication.
|
| Jobs Created |
0.00 |
| Description of Jobs Created |
This award provides the funds for our laboratory to purchase a widefield fluorescence microscope with specialized software, in order to accelerate our studies of how cells communicate with each other. We anticipate that the purchase of this microscope will have a positive impact on maintaining the jobs of the American citizens who work for the vendor, MVI Inc. of Avon, Massachusetts, including sales and service representatives, as well as the shipping and moving companies that handle delivery of the instrument to Charlestown, MA, and transport within our building. |
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
75-0852 |
| Award Information |
| Award Date |
09/18/2009 |
| Award Number |
3R01GM060501-10A1S1 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
75 |
| Funding Agency Name |
Department of Health and Human Services |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
75 |
| Awarding Agency Name |
Department of Health and Human Services |
| Amount of Award |
$99,994 |
| Funds Invoiced/Received |
$99,994 |
| Expenditure Amount |
$99,994 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
622110 |
| Activity Description |
General Medical and Surgical Hospitals |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
1 |
| Total Amount of payments to vendors greater than $25,000/award |
$99,985 |
| Number of payments to vendors less than $25,000/award |
4 |
| Total Amount of payments to vendors less than $25,000/award |
$18,853 |
Micro Video Instruments, Inc. - Award Number 3R01GM060501-10A1S1 - Micro Video Instruments, Inc.
| Award Number |
3R01GM060501-10A1S1 |
| Sub-Award Number |
N/A |
| Vendor DUNS Number |
786893206 |
| Vendor HQ Zip Code + 4 |
02322-1100 |
| Vendor Name |
Micro Video Instruments, Inc. |
| Product and Service Description |
Nikon 90i Automated microscope with time lapse ? for research on interactions between morphogens in the transforming growth β (TGFβ) factor family and those that stimulate the receptor tyrosine kinase (RTK) pathway
|
| Payment Amount |
$99,985 |
| Location Information |
| Latitude, Longitude |
42º 21' 44",
-71º 4' 11" |
| Congressional District |
09 |
| Address 1 |
55 Fruit Street |
| Address 2 |
|
| City |
Boston |
| County |
Suffolk |
| State |
MA |
| Zip |
02114-0000 |
|
 |