Permanent damage to organs and their constituent parts is a major cause of human morbidity. While the need for organ regeneration is partly addressed by transplantation and bioengineered materials and devices, the development of a systematic method to generate new organs and organ parts would transform medicine. At present, however, there is no unified discipline that integrates knowledge about organogenesis, gene regulatory networks, progenitor cells and tissue engineering into a systematic, non-empiric framework that can be used to synthesize organs in vitro. Despite their different functions, many mammalian organs develop by common mechanisms that involve the sequential, ordered exchange of signals befween interacting cell populations, resulting in their progressive differentiation. We hypothesize that the complex, dynamic regulatory networks that underlie endogenous organ development can be resolved at the genetic and ultimately molecular level by the integration of different scientific disciplines, and that this information can be used in the form of a """"""""molecular blueprint"""""""" to design and build organ precursors and parts. The Systems-based Consortium for Organ Design and Engineering (SysCODE) will focus on the synthesis of three murine organ components: the tooth germ, pancreatic islet and heart valve. These developing tissues represent both graded levels of complexity and the acquisition of distinct mechanical, physiologic and dynamic properties. To accomplish this ambitious goal, the Consortium will require the formation of new interdisciplines that lie at the nodal points between developmental biology, computational and genome science, and tissue engineering. To this end, we have recruited 24 exceptional scientists from Harvard and its affiliated Hospitals, MIT, Vanderbilt and Boston University who encompass the necessary expertise and who share a common vision of working together as an integrated scientific team to achieve this compelling goal. This U54 Leadership and Management Module describes the grand challenge of organ engineering, the scientific and administrative components that this Consortium has now assembled to meet the challenge, and the strategic plan for how this Consortium will do so. This Consortium will lead in the development of a new paradigm for interdisciplinary science, and build organ'parts in a way that will transform medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Linked Specialized Center Cooperative Agreement (UL1)
Project #
3UL1DE019581-02S1
Application #
7659088
Study Section
Special Emphasis Panel (ZRR1-SRC (99))
Program Officer
Riddle, Melissa
Project Start
2007-09-20
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$48,809
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Barkal, Amira A; Srinivasan, Sharanya; Hashimoto, Tatsunori et al. (2016) Cas9 Functionally Opens Chromatin. PLoS One 11:e0152683
Hashimoto, Tatsunori; Sherwood, Richard I; Kang, Daniel D et al. (2016) A synergistic DNA logic predicts genome-wide chromatin accessibility. Genome Res 26:1430-1440
Arbab, Mandana; Srinivasan, Sharanya; Hashimoto, Tatsunori et al. (2015) Cloning-free CRISPR. Stem Cell Reports 5:908-917
Sherwood, Richard I; Hashimoto, Tatsunori; O'Donnell, Charles W et al. (2014) Discovery of directional and nondirectional pioneer transcription factors by modeling DNase profile magnitude and shape. Nat Biotechnol 32:171-178
Arbab, Mandana; Mahony, Shaun; Cho, Hyunjii et al. (2013) A multi-parametric flow cytometric assay to analyze DNA-protein interactions. Nucleic Acids Res 41:e38
O'Connell, Daniel J; Ho, Joshua W K; Mammoto, Tadanori et al. (2012) A Wnt-bmp feedback circuit controls intertissue signaling dynamics in tooth organogenesis. Sci Signal 5:ra4
Zhang, Xiaohui; Khimji, Imran; Shao, Lei et al. (2012) Nanoliter droplet vitrification for oocyte cryopreservation. Nanomedicine (Lond) 7:553-64
Anchan, Raymond M; Quaas, Philipp; Gerami-Naini, Behzad et al. (2011) Amniocytes can serve a dual function as a source of iPS cells and feeder layers. Hum Mol Genet 20:962-74
Wang, Xiu-Ping; O'Connell, Daniel J; Lund, Jennifer J et al. (2009) Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development 136:1939-49