2005 — 2006 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Light Induced Signaling in Lov Domains @ University of Illinois Urbana-Champaign |
1 |
2006 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Molecular Mechanism of Pcra Helicase @ University of Illinois Urbana-Champaign |
1 |
2008 — 2009 |
Dittrich, Markus |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Spatially Realistic Simulations of Calcium Dependent Neurotransmitter Release. @ Carnegie-Mellon University
DESCRIPTION (provided by applicant): The proposed research aims to develop a comprehensive and spatially realistic computational model of action potential triggered, calcium dependent neurotransmitter release from synaptic vesicles. This model will provide unprecedented spatio-temporal insights into the physiological processes following the invasion of an action potential into a nerve terminal. Model development will proceed from an existing, spatially realistic baseline model of a single active zone, the specialized region within a nerve terminal that includes neurotransmitter release machinery. All simulations will be carried out with the program MCell which uses Monte Carlo algorithms to simulate molecular diffusion of calcium ions and buffer molecules, binding of calcium ions to receptors, and calcium channel gating inside arbitrary complex cellular spaces. Guided by experimental input, we will investigate the effect of perturbations and combinations thereof to the existing baseline model such as changes in the location, arrangement (homogeneous, randomized, clustered), and number of calcium channels;drug treatments (3,4-diaminopyridine, roscovitin) influencing the calcium channel kinetics and action potential shape;toxin treatments blocking fractions of calcium channels;and the effect of mobile buffer and/or mixtures of static and mobile buffer on vesicle release. These studies will lead to significant improvements of the baseline model and, thereby, set the stage for an investigation of short term synaptic plasticity via paired pulse action potentials. We will first identify mechanisms that give rise to the experimentally observed values for paired pulse facilitation and then investigate the effect of changes in the interstimulus interval and drug treatments on paired pulse facilitation. Clearly, the importance of elucidating the key elements of paired pulse facilitation and thereby synaptic plasticity for a more comprehensive understanding of human neural function can not be underestimated. The proper and faithful transmission of nerve signals along neurons in the human body is crucial for survival. Synapses constitute the connecting elements between neurons and cells they innervate and many debilitating neurological disorders are caused by synaptic dys-function. Hence, a proper understanding of synaptic function is crucial for the development of clinical treatments for neurological diseases. The proposed research will directly contribute to our understanding of synaptic function and is therefore directly relevant to the mission of the NIH.
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0.937 |
2009 — 2013 |
Stiles, Joel Dittrich, Markus |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Calcium Entry and Transmitter Release At the Frog Nmj @ Carnegie-Mellon University
Cells in the nervous system communicate at specialized regions called synapses. When a nerve fires, calcium ions enter synapses from the surrounding extracellular fluid and cause neurotransmitter molecules to be released into the synaptic cleft between the communicating cells. However, the sequence of molecular events leading from calcium entry to transmitter release remains unknown. To better understand this important process, this research will combine laboratory experiments and large-scale computer simulations to build detailed 3-D models of calcium-triggered neurotransmitter release at the synapse between a nerve and muscle cell in the frog. In many respects, the frog synapse is quite similar to many mammalian synapses (including human), and yet it presents unique opportunities for combined laboratory and computational studies. This makes it an ideal choice for creation of highly realistic and accurate models. Using these models, hypotheses will be developed and tested to explain how synapses use calcium to trigger neurotransmitter release, and how repeated nerve firing changes release, as occurs at all synapses as they respond to changing behavioral conditions. Development of realistic 3-D computer models also presents unique opportunities for transformational training and education. Undergraduate, graduate, and postdoctoral trainees will participate directly in these studies, and high quality animations of the models will be adapted for use in the classroom. The project co-directors (S. Meriney, Univ. of Pittsburgh, and J. Stiles, Carnegie Mellon Univ.) and faculty colleagues will use the new teaching material at the University of Pittsburgh, the Pittsburgh Supercomputing Center, and Carnegie Mellon University, in undergraduate and graduate Neuroscience, Biology, and Computational Biology courses, a multi-institutional summer institute (www.ccbb.pitt.edu/bbsi), workshops, and web-based tutorials (www.mcell.psc.edu/tutorials/tlist.htm). New teaching material will also be featured in the CMIST program, an undergraduate and K-12 outreach program at the National Resource for Biomedical Supercomputing, directed by Dr. Stiles (www.nrbsc.org/cmist).
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0.937 |
2010 — 2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Anton Grant For Friendly Users to Test @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. friendly grant for Anton testing
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0.937 |
2010 — 2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
De Shaw Research Group Access @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Grant for D.E. Shaw staff to access Anton
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0.937 |
2010 |
Dittrich, Markus |
RC2Activity Code Description: To support high impact ideas that may lay the foundation for new fields of investigation; accelerate breakthroughs; stimulate early and applied research on cutting-edge technologies; foster new approaches to improve the interactions among multi- and interdisciplinary research teams; or, advance the research enterprise in a way that could stimulate future growth and investments and advance public health and health care delivery. This activity code could support either a specific research question or propose the creation of a unique infrastructure/resource designed to accelerate scientific progress in the future. |
Innovative Supercomputing For Breakthrough Molecular Dynamics @ Carnegie-Mellon University
DESCRIPTION (provided by applicant): A partnership between D.E. Shaw Research (DESRES) and the National Resource for Biomedical Supercomputing (NRBSC) at the Pittsburgh Supercomputing Center (PSC) will enable breakthrough advances in Molecular Dynamics (MD) research. DESRES has recently developed new supercomputing technology that can accelerate MD simulations by about 100-fold. For this project, DESRES has offered a gift of community access to one of their supercomputers (Anton) hosted at the NRBSC/PSC. This gift is truly unprecedented, and would allow the MD research community to investigate important outstanding questions on scales of biological time that up until now have been completely inaccessible. Many important biomolecular processes occur over times on the order of milliseconds. MD simulations provide insights into the behavior of proteins, cell membranes, RNA, and DNA at an atomic level of detail, but with discrete time steps on the order of femtoseconds (10-15 seconds), current simulations typically can reach no more than about 100 nanoseconds of biological time per day of wall-clock time for medium-size molecular systems. Thus, most existing MD simulations remain in the nanosecond range of simulated time, with only a few runs extending to a microsecond. In contrast, an Anton prototype is now able to run simulations of comparable molecular systems at rates about two orders of magnitude faster. Such dramatic acceleration could literally transform the way that molecular structure and function are studied. For the first time, scientists might visualize and predict critically important biochemical phenomena, including the structural changes that underlie protein function, and the interactions between two proteins or between a protein and a candidate drug molecule. At that level, MD simulations could begin to answer important open biomedical questions, contribute substantially to drug development, and provide direct inputs to simulations of cells and tissues run with Brownian Dynamics and related stochastic diffusion-reaction algorithms at even longer time-scales. In this highly innovative project, DESRES and the NRBSC will partner to make an Anton supercomputer available to the national research community. A national allocation mechanism will be implemented, and powerful new open-source data analysis methods will be developed as well. This project will enable breakthrough science, and may also usher in a new era of specialized computers developed for biomedical modeling and simulation, spanning molecular to cellular and tissue scales of space and time. PUBLIC HEALTH RELEVANCE: New supercomputing technology, approximately one hundred times faster than pre-existing resources, will be made available to the national research community for the first time ever. This new technology will enable breakthrough advances in the modeling and simulation of molecular structure and function (Molecular Dynamics). Such dramatic acceleration may literally transform the way that scientists visualize and predict important chemical interactions that underlie health and disease, including how protein structure changes as the molecules carry out their functions, and how protein molecules bind to new candidate drug molecules. These advances will be made possible through a partnership between D.E. Shaw Research and the National Resource for Biomedical Supercomputing at the Pittsburgh Supercomputing Center.
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0.937 |
2010 — 2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Workshop: Computational Biophysics Using Namd and Vmd Workshop Dates: 5/10-5/1 @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Workshop: Computational Biophysics using NAMD and VMD workshop Dates: 5/10-5/14/10 We are doing this workshop in conjunction with the Univ. of IL Champaign-Urbana's Theoretical and Computational Biophysics Group (Klaus Schulten's group)
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0.937 |
2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Group For Queue Privs For Anton Awardees @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. group to allow anton users to submit jobs to 512 Anton platform
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0.937 |
2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Group For Queue Privs For Anton Grants That Have Consumed Their Allocations @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Low priority queue for Anton grants that have consumed their allocations
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0.937 |
2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Workshop For First Phase Anton Awardees @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Workshop for first phase Anton Awardees
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0.937 |
2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Workshop For Second Phase Anton Awardees @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Workshop for second phase Anton Awardees
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0.937 |
2011 |
Dittrich, Markus |
P41Activity Code Description: Undocumented code - click on the grant title for more information. |
Workshop: Computational Biophysics Using Namd and Vmd Workshop Dates: 5/16-5/1 @ Carnegie-Mellon University
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. NAMD/VMD workshop
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0.937 |
2014 — 2016 |
Blanpied, Thomas A (co-PI) [⬀] Dittrich, Markus Meriney, Stephen D [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Crcns: Transmitter Release Site Organization in Plasticity and Disease At the Nmj @ University of Pittsburgh At Pittsburgh
DESCRIPTION (provided by applicant): Communication between cells in the nervous system underlies all complex behaviors, and occurs at specialized regions of the nerve cell called synapses. Synapses work by releasing chemical transmitter from a region called the active zone, which activates a neighboring cell. We propose to characterize the relationship between active zone function and structural organization within frog and mouse neuromuscular synapses. We hypothesize that neuromuscular active zones are assembled from a basic transmitter release building block: the unreliable single-vesicle release site consisting of a docked synaptic vesicle and its associated Ca2+ channels. We further hypothesize that major aspects of synaptic function and presynaptic homeostatic plasticity can be explained by changes in the number and organization of these single-vesicle release sites within active zones. Our approach is characterized by a seamless collaboration between three labs with expertise in computer simulations of cellular physiology (Dittrich lab), synaptic anatomy, physiology, and Ca2+ imaging (Meriney lab), and super-resolution imaging of the number and spatial distribution of synaptic proteins (Blanpied lab). Importantly, as part of this proposal, trainees from all three laboratories will receive crosstraining in each lab. We will use this collaborative approach to develop a comprehensive MCell computer model of the presynaptic transmitter release site that will significantly increase our understanding of the relationship between active zone organization and synaptic function. This insight will not only lead to a better understanding of presynaptic mechanisms of homeostatic plasticity but also aid in our understanding of synaptic diseases, which are known to underlie a large number of neurological disorders. Intellectual Merit: A significant number of neurological diseases are known to affect the synapse by targeting synaptic organization and function. While most research on this important topic has to date focused on postsynaptic adaptations, it has become increasingly clear that presynaptic homeostatic changes are likely to be just as important. Thus, a better understanding of the role of presynaptic structure and organization in synaptic function under both control and disease conditions is needed. Broader Impacts: The MCell model that we will develop will enhance our teaching mission in many ways. It will provide an example of unprecedented scale and realism for the illustration of nerve terminal structure and function. This material will be used in courses and programs at the University of Pittsburgh, the University of Maryland, and Carnegie Mellon University. These include undergraduate and graduate Neuroscience courses, a Computational Biology PhD program that spans PITT and Carnegie Mellon University, summer workshops, and web-based tutorials (www.mcell.org). These simulations will expand previous models that already have been converted into instructive 3D movies, which are routinely shown to a broad range of audiences during open houses, student visits or classroom teaching. This work will also provide source material for teaching examples tailored to high school outreach programs at the Pittsburgh Supercomputing Center, particularly the CMIST program (Computational Modules in Science Teaching, www.cmist.org) of the National Resource for Biomedical Supercomputing (NRBSC) directed by Dr. Dittrich. Our proposed work will have a broad impact on K-12 education, undergraduate teaching and training, graduate and post-graduate training, community outreach, STEM teaching, training at underrepresented minority institutions, and knowledge of synaptic function in the field. Dr. Meriney is a member of the Neuroscience outreach committee at the University of Pittsburgh (PITT), which organizes a variety of community events. Dr. Meriney's laboratory is in the Arts and Sciences College, so the proposed research would contribute to undergraduate teaching via undergraduate research participation in the proposed work, and changes to content for undergraduate courses based on new research insights. Dr. Dittrich will also train undergraduate students in his laboratory as participants in the proposed work. He is training faculty in the NSF funded TECBio REU program at the PITT and typically mentors 1-2 students in computational projects as part of the program. In addition, Dr. Dittrich is a training faculty in the PA Governors School for the Sciences, an intense summer program for talented high school students in Pennsylvania. Drs. Dittrich, Meriney, and Blanpied will bring graduate researchers and postdoctoral fellows into their labs who will directly participate in the proposed experiments, receive cross training in all three laboratories, and receive career training. Lastly, Dr. Ulises Ricoy (an under-represented minority faculty member) from Northern New Mexico College will visit during each summer to learn new research, teaching, and training tools to bring back to underrepresented minority undergraduates at Northern New Mexico College. This will expose these underrepresented minority students to an intense academic research environment and aid in their training and career planning.
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0.948 |