HHS Recovery Act Recipient Reporting Readiness Tool

Step 4. Review and Copy the Grant Awards Data

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Prime Recipient Report

Award Detail for: INTEGRATED MULTI-SCALE ADHESIVE DYNAMICS MODELING OF T-LYMPHOCYTE HOMING
Recipient Name:UNIVERSITY OF PENNSYLVANIA
DUNS Number: 042250712
3451 WALNUT STREET
PHILADELPHIA, PA 19104-6205

Reporting Information

Award Type*: Grant

Award Number*: 5R01AI082292-02

Final Report*: Recipient responsible for this data

Award Recipient Information

Recipient DUNS Number*: 042250712

Recipient Account Number: Recipient responsible for this data

Recipient Congressional District*: 1

Award Information

Funding Agency Code*: 7529

Awarding Agency Code*:7529

Award Date*: 06-14-2010

Amount of Award*: $ 385,555

Program Source (TAS)*: 750900

CFDA Number*: 93.701

Sub Account Number for Program Source (TAS)*: Recipient responsible for this data

Total Number of Sub Awards to Individuals*: Recipient responsible for this data

Total Amount of Sub Awards to Individuals*: Recipient responsible for this data

Total Number of Payments to Vendors less than $25,000/award*: Recipient responsible for this data

Total Amount of Payments to Vendors less than $25,000/award*: Recipient responsible for this data

Total Number of Sub Awards less than $25,000/award*: Recipient responsible for this data

Total Amount of Sub Awards less than $25,000/award*: Recipient responsible for this data

Award Description* DESCRIPTION (provided by applicant): The proper functioning of the immune system relies on T-lymphocytes to travel throughout the body and home to specialized tissues to transfer molecular information. Intimate molecular communication between cells is crucial to immune cells' maturation and activation. It has been established that lymphocyte trafficking from the blood stream and the lymphatic vessels into tissues is controlled by molecular "zip-codes" that identify the location where lymphocytes need to adhere. The zip-codes are precise, quantitative combinations of adhesion molecules and chemokines/chemokine receptor pairs on the lymphocyte and host tissue, such that when there is a "match", the lymphocyte responds by adhering rapidly. The goal of this proposal is to develop novel computational tools to understand how lymphocytes integrate and convert molecular signals into the activation of leukocyte integrins to mediate specific adhesion under flow. The basis of these tools is the integration of signal transduction networks, either involving chemokine activation of G-proteins networks or the assembly of the SLP-76 dependent "signalosome', into Adhesive Dynamics, a simulator of cell adhesion. This integrated method, called Integrated Signaling Adhesive Dynamics (ISAD) can readily predict the rate of lymphocyte firm adhesion under flow. The aims of this proposed work are to 1) extend our modeling of lymphocyte signal transduction networks to both chemokine signaling and the signalosome; 2) to integrate these models into ISAD simulations to simulate the progressive rolling and stopping of lymphocytes on defined molecular substrates; and 3) to compare our simulations with the adhesive behavior of engineered T- lymphocytes, including Jurkat cells and T cells from knock-out mice in which SLP-76 is deleted or altered, or in which diacylglycerol kinases (DGK) have been deleted. We show preliminary results that SLP-76 defects lead to a decrease in adhesiveness, and DGK defects lead to an increase in adhesiveness. The gain of function of DGK mutants is recapitulated by simulations, confirming the validity of our modeling. We will also measure and simulate how multiple chemokine signals are integrated within a single cell to give rise to adhesion, and how knock-downs of key signaling components both in T-cells and immortalized T-cells (Jurkat cells) lead to quantitative alterations in adhesion. Our comparison between simulation and experiment, and extensive sensitivity analysis, will allow us to identify ranges of parameter values consistent with experimental observations and to elucidate the key controlling pathways in lymphocyte adhesion and homing. PUBLIC HEALTH RELEVANCE: Integrated Multi-scale Adhesive Dynamics Modeling of T-lymphocyte Homing Daniel A. Hammer (PI), Gary T. Koretzky (co-PI) Relevance Human immunity requires that lymphocytes travel to specific locations within the body. The homing of lymphocyte sublines is controlled through a complex molecular zip-coding, in which surface receptors on lymphocytes bind ligands on blood vessel walls, and signals inside of lymphocytes control the trafficking patterns of lymphocytes. The goal of this proposal is to develop a computational framework for modeling the interplay between adhesion and lymphocyte signal transduction to gain a better understanding of the factors that control lymphocyte homing and hence the proper response of the immune system.

Project Information

Project Name or Project/Program Title*: INTEGRATED MULTI-SCALE ADHESIVE DYNAMICS MODELING OF T-LYMPHOCYTE HOMING

Project Status*: Recipient responsible for this data

Total Federal Amount of ARRA Funds Received/Invoiced*: Recipient responsible for this data

Number of Jobs*: Recipient responsible for this data

Description of Jobs Created*: Recipient responsible for this data

Quarterly Activities/Project Description*: Recipient responsible for this data

Activity Code (NAICS or NTEE-NPC)*: Recipient responsible for this data

Total Federal Amount of ARRA Expenditure* (Enter the cumulative total amount of Recovery Funds received that were expended to projects or activities. Refer to the Data Model for details on how to calculate this amount.): Recipient responsible for this data

Total Federal ARRA Infrastructure Expenditure Recipient responsible for this data

Infrastructure Contact Name: Recipient responsible for this data

Infrastructure Contact Email: Recipient responsible for this data

Infrastructure Contact Phone: Recipient responsible for this data

Infrastructure Contact Phone Ext: Recipient responsible for this data

Infrastructure Contact Street Address 1: 3451 WALNUT STREET

Infrastructure Contact Street Address 2: Not Available

Infrastructure Contact Street Address 3: Recipient responsible for this data

Infrastructure City: PHILADELPHIA

Infrastructure State: PA

Infrastructure ZIP Code+4: 19104-6205

Infrastructure Purpose and Rationale (If applicable, enter an explanation about how the infrastructure investment will contribute to one or more purposes of the Recovery Act. Refer to the Data Model for details on what to report. 4000 characters or less.): Recipient responsible for this data

Primary Place of Performance

Street Address 1: SKIRKANICH HALL

Street Address 2: PHILADELPHIA

City*: PHILADELPHIA

State*: PA

ZIP Code+4*: 19104291

Congressional District*: 2

Country*: US

Recipient Highly Compensated Officers

Prime Recipient Indication of Reporting Applicability*: Recipient responsible for this data

1. Officer Name and Compensation: Recipient responsible for this data
2. Officer Name and Compensation: Recipient responsible for this data
3. Officer Name and Compensation: Recipient responsible for this data
4. Officer Name and Compensation: Recipient responsible for this data
5. Officer Name and Compensation: Recipient responsible for this data

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