Stem-cell Engineering; Nanocrystal-based Imaging

BioTechniques and NIH Sales have varied their approach this month to review the grants made by the National Institutes of Health over a 30-day period. Here are some highlights from among the 100 largest R01 and the 100 largest R03 grants awarded in June 2008.

Engineered Cardiac Morphogenesis–Stem Cells and Scaffolds $1,974,136

(5R01HL064387-08, National Heart, Lung, and Blood Institute)

Buddy D. Ratner (University of Washington, Seattle, WA)

Goal: To build on earlier results and develop an engineering system for clinical repair of damaged heart muscle. Specifically, the project uses proliferating human cardiomyocytes and a novel pro-angiogenic porous scaffold to engineer 300 µm diameter rods of cardiac muscle (RCM) or particles of cardiac muscle (PCM) that can be injected into a heart infarct zone and facilitate functional repair of cardiac muscle.

Probing Tumor Microenvironment Using Nanotechnology $1,692,884

(1R01CA126642-01A1, National Cancer Institute)

Rakesh K. Jain (Massachusetts General Hospital, Boston, MA)

Goal: To exploit emerging advances in semiconductor nanocrystal-based biomedical imaging to probe the tumor microenvironment and develop therapeutic and diagnostic strategies, combining intravital imaging, molecular tools and quantum dot technology, and unique in vitro, in vivo, and mathematical models. The cornerstone of the project will develop novel nanocrystal (quantum dot) constructs, biosensors, and immunoconjugates, creating “smart” nanocrystal probes of chemical and morphological environments.

Nanotechnology Linking Biomarkers with Cancer Behavior $1,309,745

(5R01CA108468-05, National Cancer Institute)

Shuming Nie (Emory University, Atlanta, GA)

Goal: To develop biomedical nanotechnology (e.g., molecular beacons, semiconductor quantum dots, and enhanced Raman probes), biomolecular engineering, and bioinformatics tools for linking molecular signatures of cancer and the host microenvironment with cancer behavior and clinical outcome, with particular focus on the biology of human prostate cancer and its clinically lethal phenotypes.

Transcriptional Regulatory Networks in Living Cells $1,294,654

(5R01HG002668-05, National Human Genome Research Institute)

Richard A. Young (Whitehead Institute for Biomedical Research, Cambridge, MA)

Goal: To map the transcriptional regulatory circuitry controlling gene expression in embryonic stem cells and selected differentiated cells, beginning with identifying active and silent portions of the genome and determining how master regulators control a core set of genes, and moving on to define active and repressed chromatin structure for the entire non-repeat genome and identify the core regulatory circuitry that defines cellular phenotype.

Studies on Transfer RNA $1,263,914

(5R01GM022854-33, National Institute of General Medical Sciences)

Dieter G. Soll (Yale University, New Haven, CT)

Goal: To provide a detailed and integrated description of aminoacyl-tRNA synthesis and its myriad roles in extant organisms by exploring alternative routes of aminoacyl-tRNA synthesis: a) cysteinyl-tRNA synthesis in methanogenic archaea, b) pyrrolysyl-tRNA synthesis by an aminoacyl-tRNA synthetase-like uncharacterized enzyme, and c) asparaginyl-tRNA synthesis and glutaminyl-tRNA synthesis by the three kingdomspecific tRNA-dependent amidotransferases.

Vitrification of Recombinant Non-Beta Cells in Constructs $94,993

(5R03EB004671-02, National Institute of Biomedical Imaging and Bioengineering)

Ying Song (Xytex Research, Inc., Augusta, GA)

Goal: To develop a method for effective long-term storage and transportation of ex vivo–engineered human cells for reimplantation in the patient to treat diabetes. This proposal extends testing of vitrification as a storage method for tissue-engineered pancreas to include genetically engineered pancreatic models (human HepG2 cells). The program will screen new methods of molecular ice control.