1977 — 1980 |
Salmon, Edward |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Mechanisms of Mitotic Spindle Assembly and Chromosome Movement @ University of North Carolina At Chapel Hill |
0.915 |
1985 — 2018 |
Salmon, Edward 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. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Mechanisms of Mitotic Spindle Assembly and Function @ University of North Carolina Chapel Hill
DESCRIPTION (provided by applicant): The major focus for the next period of this grant will be spindle, kinetochore and centromere protein mechanisms that act to achieve accurate chromosome segregation. Accuracy is critical because the missegregation of even one chromosome produces aneuploidy that can lead to cancer or developmental defects. Kinetochores have at least five key roles in assuring accurate segregation: 1) they produce a diffusible signal for the spindle checkpoint to delay anaphase until sister kinetochores are properly attached by MTs to opposite poles and aligned on the metaphase plate; 2) they provide stable, but dynamic, attachment to MT plus ends to turn off spindle checkpoint activity and prevent errors in MT attachment; 3) they act as a force-generating depolymerase for movement of chromosomes poleward coupled to plus-end depolymerization of kMTs at the kinetochore; 4) they provide a tension-sensitive slip clutch, generating tension from the poleward flux of kMTs while maintaining attachment to polymerizing plus ends of MTs during kinetochore movements away from the pole, and 5) they correct errors in MT attachment so that the formation of kMTs to opposite poles (merotelic orientation) does not result in lagging chromosomes and mis-segregation in anaphase. Centromere passenger proteins, which are located on the inner centromere behind the kinetochore, also appear to regulate kMT attachment and MT-dependent signaling of the cortical site for cytokinesis. Most of our studies focus on protein function in mammalian tissue cells, but budding yeast mitotic kinetochores and shmoo tips are useful genetic models for understanding protein function at dynamic plus-end attachment sites. A major strength of our program has been, and will continue to be, the development and application of new microscopy techniques for measurements of protein function in living cells and reconstituted preparations.
|
0.936 |
1987 — 1989 |
Salmon, Edward |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Uv Microbeam Analysis of Microtubule Dynamics @ University of North Carolina At Chapel Hill
Before cells divide, their genetic information, contained in structures called chromosomes, is duplicated precisely. During cell division, the duplicated chromosomes are distributed into the two daughter cells so that each daughter subsequently contains exactly the same kind and number of chromosomes. The cellular organelles responsible for carrying out this crucial process are collectively called the mitotic spindle. The spindle is composed primarily of a complex network of microtubule cables that attach to individual chromosomes at one end, and become anchored at their other end to sites called the cell poles. During the course of cell division these cables somehow pull the chromosomes to their respective poles, by a mechanism whose details are only poorly understood. In this novel and well written proposal, the principal investigator will design, construct, and calibrate an ultraviolet microbeam apparatus. This device is capable of irradiating and thereby cutting a single microtubule fiber in a living cell. The experiments described will allow the investigator to distinguish between several current models of microtubule function during chromosome movement. This is the case because the various models made different predictions with respect to the effect of gap production on the stability and dynamics of the fiber, the movement of chromosomes, and the nature of irradiation-induced gap repair.
|
0.915 |
2000 — 2007 |
Salmon, Edward 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. |
Fluorescent Speckle Microscopy @ University of North Carolina Chapel Hill
[unreadable] DESCRIPTION (provided by applicant): Fluorescent speckle microscopy (FSM) is a technique we initially developed for measuring the movements and sites of polymerization/depolymerization of individual microtubules (MTs) and arrays of actin filaments in motile tissue culture cells and the poleward flux of MTs within spindle fibers during mitosis. Assembly of these polymers from a pool containing a low percentage of fluorescently labeled subunits (about 1% or less) produces a random distribution of fluorophores along the polymer lattice that produces "fluorescent speckle" fiduciary marks varying from zero to several fluorophores (5-8) within the diffraction limited resolution of the microscope. The major focus of this application is on the further development of the FSM method for the analysis of MT function in spindle mechanics. In particular, how MT and kinetochore proteins function in spindle assembly, chromosome alignment and accurate chromosome segregation. This requires the development of new FSM microscope technology for the rapid recording of multi-wavelength and 3-D time-lapse images of MT fluorescent speckles relative to fluorescent marks or speckles at kinetochores, poles, MT associated proteins (MAPs), motor proteins and MT ends. A major next step for FSM to become a powerful analytical tool for these systems is the development of new Computer Vision methods for obtaining quantitative information about polymer movement and turnover in 2-D and 3-D at high resolution relative to the other molecular fluorescent markers in the spindle. To study protein function, we are particularly interested in optimizing FSM for genetic model organisms including budding yeast, for the biochemically accessible Xenopus egg extracts and for siRNA with mammalian tissue cells. Experience gained in the course of these studies will be used to direct and refine hardware and software development. [unreadable] [unreadable]
|
0.936 |
2000 — 2004 |
Salmon, Edward Washburn, Sean Superfine, Richard Taylor, Russell Cheney, Richard (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Xyz On a Chip: Biomolecular Motor/Nanotube Integration For Actuator Nanotechnology @ University of North Carolina At Chapel Hill
0088509 Superfine The goal of this research is to study the control over molecular motors with an engineering applications perspective, exploring ways in which these machines can be used in designed systems, e. g., the synthesis and delivery of pharmacological agents. The specific goals of this research are to: (1) demonstrate the control of the patterning of motor raceways as functioning tracks for the motion of motor proteins, (2) study the two main classes of proteins actin/myosin and microtubule/kinesin to understand their relative merits towards nanotechnology applications, (3) study the application of single motors and collections of motor proteins, (4) study the coupling of nanotubes to electrical circuitry through electro/dielectrokinesis at the nonometer scale, and (5) understand a processing methodology for incorporating nanometer scale ebeam lithography, nanotube placement/growth, patterned chemical functionalization and motor binding and motility. This award is co-funded by the Division of Engineering Education and Centers, the Division of Chemical and Transport Systems, and the Division of Bioengineering and Environmental Systems.
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0.915 |
2009 — 2013 |
Salmon, Edward D. |
R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Mechanisms of Mictotic Spindle Assembly and Function @ Univ of North Carolina Chapel Hill
The major focus for the next period of this grant will be spindle, kinetochore and centromere protein mechanisms that act to achieve accurate chromosome segregation. Accuracy is critical because the mis- segregation of even one chromosome produces aneuploidy that can lead to cancer or developmental defects. Kinetochores have at least five key roles in assuring accurate segregation: 1) they produce a diffusible signal for the spindle checkpoint to delay anaphase until sister kinetochores are properly attached by MTs to opposite poles and aligned on the metaphase plate;2) they provide stable, but dynamic, attachment to MT plus ends to turn off spindle checkpoint activity and prevent errors in MT attachment;3) they act as a force- generating depolymerase for movement of chromosomes poleward coupled to plus-end depolymerization of kMTs at the kinetochore;4) they provide a tension-sensitive slip clutch, generating tension from the poleward flux of kMTs while maintaining attachment to polymerizing plus ends of MTs during kinetochore movements away from the pole, and 5) they correct errors in MT attachment so that the formation of kMTs to opposite poles (merotelic orientation) does not result in lagging chromosomes and mis-segregation in anaphase. Centromere passenger proteins, which are located on the inner centromere behind the kinetochore, also appear to regulate kMT attachment and MT-dependent signaling of the cortical site for cytokinesis. Most of our studies focus on protein function in mammalian tissue cells, but budding yeast mitotic kinetochores and shmoo tips are useful genetic models for understanding protein function at dynamic plus-end attachment sites. A major strength of our program has been, and will continue to be, the development and application of new microscopy techniques for measurements of protein function in living cells and reconstituted preparations.
|
0.924 |