MASSACHUSETTS GENERAL HOSPITAL, THE
The research will result in a better understanding of the mechanisms by which general anesthetics act on ligand-gated ion channels. This provides the scientific foundation upon which anesthetics with higher affinity and lower toxicity may be developed. In addition, the methods developed will have wide applicability because many other classes of drugs act on these channels.
| AWARD OVERVIEW |
| Award Number |
3P01GM058448-11S1 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$88,534 |
Project Location - City |
Boston |
| Award Date |
06/04/2010 |
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 |
General Anesthetic Sites on Ligand Gated Ion Channels |
| Project Status |
Completed |
| Final Project Report Submitted |
Yes |
| Project Activities Description |
General Medical and Surgical Hospitals |
| Quarterly Activities/Project Description |
This quarter we have moved on to examine a new receptor that the Protein Production Core of the Program Project Grant has recently expressed at high-levels. This is a heterologous GABA(A) receptor containing the alpha1-, the beta3- and the gamma2-subunits. Even when purified receptors have been used, these subunits are not well separated on SDS-PAGE. To aid the analysis, we deglycosylated the receptor and were able to separate three bands on SDS-PAGE. However, these bands are not well separated and there is a good deal of overlap with each subunit being found in different proportions in each band when they were analyzed by mass spectrometry. This preliminary analysis has been very useful, because we can be sure that the gamma2-subunit is expressed (the literature castes some doubt on this in heterologous systems). The above findings are based on trypsin digests and fingerprinting the N-terminal domain of the subunits. We are now conducting experiments to sequence all domains of this receptor. Using an in-gel trypsin/chymotrypsin digest and a long HPLC-gradient prior to mass spectrometry, progress is being made. Although the complete data analysis is awaiting a software upgrade, preliminary less detailed analysis shows the coverage achieved in the alpha1 and beta3-subunits in a single experiment is comparable to, but somewhat lower than, that in GABA(A)Rs containing only alpha1- and beta3-subunits reported last quarter. However, coverage of the gamma2-subunit is disappointing. This is likely because of the stoichiometry (alpha1:beta3:gamma2, 2:2:1); there is only half the amount of gamma2-subunit. One conclusion of these studies is that in order to obtain sequences in the transmembrane domains, it is necessary to use a much larger amount of protein than that customarily employed when soluble proteins are under study by HPLC?MSMS mass spectrometry. |
| Jobs Created |
0.00 |
| Description of Jobs Created |
Dr. S. Shunmugasundararaj has been partially supported by this project starting 1 July 2010. Without this support we would be unable to continue his employment. The research will result in a better understanding of the mechanisms by which general anesthetics act on ligand-gated ion channels. This provides the scientific foundation upon which anesthetics with higher affinity and lower toxicity may be developed. In addition, the methods developed will have wide applicability because many other classes of drugs act on these channels. |
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 |
06/04/2010 |
| Award Number |
3P01GM058448-11S1 |
| 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 |
$88,534 |
| Funds Invoiced/Received |
$88,534 |
| Expenditure Amount |
$88,534 |
| 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 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
0 |
| Total Amount of payments to vendors less than $25,000/award |
$0 |
| 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 |
|
 |