- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- Mechanical Behavior of Composites
- Fungal and yeast genetics research
- Epoxy Resin Curing Processes
- Polymer composites and self-healing
- Photosynthetic Processes and Mechanisms
- Fiber-reinforced polymer composites
- Manufacturing Process and Optimization
- Trypanosoma species research and implications
- Orthopaedic implants and arthroplasty
- Microbial Metabolic Engineering and Bioproduction
- Total Knee Arthroplasty Outcomes
- Additive Manufacturing and 3D Printing Technologies
- Surface Modification and Superhydrophobicity
- Synthesis and properties of polymers
- Tribology and Wear Analysis
- Non-Destructive Testing Techniques
- RNA Research and Splicing
- Polymer crystallization and properties
- High-Velocity Impact and Material Behavior
- Photopolymerization techniques and applications
- Biochemical and Molecular Research
- Electronic Packaging and Soldering Technologies
DEVCOM Army Research Laboratory
2012-2025
United States Army Combat Capabilities Development Command
2022-2025
Worcester Polytechnic Institute
2023
Johns Hopkins University
2005-2014
Thomas Jefferson National Accelerator Facility
2014
Johns Hopkins Medicine
2003-2013
Drexel University
2009-2010
Naval Research Laboratory Materials Science and Technology Division
2007
LDS Hospital
2006
Virginia Tech
1998-2001
In yeast, mitochondrial division and fusion are highly regulated during growth, mating sporulation, yet the mechanisms controlling these activities unknown. Using a novel screen, we isolated mutants in which mitochondria lose their normal structure, instead form large network of interconnected tubules. These mutants, appear defective division, all carried mutations DNM1, dynamin-related protein that localizes to mitochondria. We also containing numerous fragments. were FZO1, gene previously...
The ultimate product of yeast mating-type interconversion is a stable a/alpha diploid cell. A haploid cell carrying the HO gene gives rise to in two-step process: first, switches mating type as result genetic rearrangement (cassette substitution) catalyzed by HO; then, cells opposite mate form diploids. Mating-type does not occur diploids despite presence gene. We have identified plasmid screening clone bank (constructed vector YEp13) for plasmids that allow switching ho cells. segment...
In Saccharomyces cerevisiae, mitochondrial fusion requires at least two outer membrane proteins, Fzo1p and Ugo1p. We provide direct evidence that the dynamin-related Mgm1 protein is also required for fusion. Like fzo1 ugo1 mutants, cells disrupted MGM1 gene contain numerous fragments instead of few long, tubular organelles seen in wild-type cells. Fragmentation mitochondria mgm1 mutants rescued by disrupting DNM1, a division. zygotes formed mating do not fuse mix their contents. Introducing...
The extent of wear retrieved, polyethylene tibial components appears to be related design. To test this observation, 122 inserts were graded for wear, and new several designs tested contact stress using Fuji film. Finite element analysis provided insight into subsurface stresses. Significant was seen in 61.5% the examined. presence unconsolidated polymer powder 44% found statistically correlated with severe articulating surface. Contact noncongruent exceed yield strength polyethylene. There...
In the yeast Saccharomyces cerevisiae, mitochondria are elongated organelles which form a reticulum around cell periphery. To determine mechanism by mitochondrial shape is established and maintained, we screened mutants for those defective in morphology. One of these mutants, mmm1, temperature-sensitive external its mitochondria. At restrictive temperature, appear to quickly collapse into large, spherical organelles. Upon return permissive wild-type structure restored. The morphology other...
Membrane fusion plays an important role in controlling the shape, number, and distribution of mitochondria. In yeast Saccharomyces cerevisiae, outer membrane protein Fzo1p has been shown to mediate mitochondrial fusion. Using a novel genetic screen, we have isolated new mutants defective their One these mutants, ugo1, shows several similarities fzo1 mutants. ugo1 cells contain numerous fragments instead few long, tubular organelles seen wild-type cells. lose DNA (mtDNA). zygotes formed by...
We have identified a new protein, Tim54p, located in the yeast mitochondrial inner membrane. Tim54p is an essential import component, required for insertion of at least two polytopic proteins into membrane, but not translocation precursors matrix. Several observations suggest that and Tim22p are part protein complex membrane distinct from previously characterized Tim23p-Tim17p complex. First, multiple copies TIM22 gene, TIM23 or TIM17, suppress growth defect tim54-1 temperature-sensitive...
In the yeast Saccharomyces cerevisiae, mitochondria form a branched, tubular reticulum in periphery of cell. Mmm1p is required to maintain normal mitochondrial shape and mmm1 mutants large, spherical organelles. To further explore function, we examined localization Mmm1p–green fluorescent protein (GFP) fusion living cells. We found that Mmm1p-GFP located small, punctate structures on outer membrane, adjacent subset matrix-localized DNA nucleoids. also temperature-sensitive mmm1-1 mutant was...
The combination of a cobalt-alloy head on titanium-alloy femoral hip stem is widely accepted for press-fit and biologic fixation applications. Examination 30 components retrieved at periods 0.5 to 66.9 months histologic examination tissue ingrowth revealed that 56.6% the tapered connections between showed evidence crevice corrosion leading concerns metal ion release potential failure fixation.
In yeast, mitochondrial fusion requires Ugo1p and two GTPases, Fzo1p Mgm1p. is anchored in the outer membrane with its N terminus facing cytosol C intermembrane space. also an protein, whereas Mgm1p located Recent studies suggest that these three proteins form protein complexes mediate fusion. Here, we show cytoplasmic domain of directly interacts Fzo1p, space binds to We identified Ugo1p-binding site demonstrated Ugo1p-Fzo1p interaction essential for formation shape, maintenance DNA,...
Self-healing materials are particularly desirable for load-bearing applications because they offer the potential increased safety and material lifetimes. A furan-functionalized polymer network was designed that can heal via covalent bonding across crack surface with use of a healing agent consisting bismaleimide in solution. Average efficiencies approximately 70% were observed. The ability fiber-reinforced composite specimens investigated flexural, short beam shear, double cantilever...
Precise targeting of mitochondrial precursor proteins to mitochondria requires receptor functions Tom20, Tom22, and Tom70 on the surface. Tom20 is a major import that recognizes preferentially presequences, specialized presequence-less inner membrane proteins. The cytosolic domain Tom22 appears function as in cooperation with but how its substrate specificity differs from remains unclear. To reveal possible differences specificities between if any, we deleted or vitro by introducing cleavage...
Mitochondria are dynamic organelles that undergo frequent division and fusion, but the molecular mechanisms of these two events not well understood. Dnm1p, a mitochondria-associated, dynamin-related GTPase was previously shown to mediate mitochondrial fission. Recently, genome-wide yeast two-hybrid screen identified an uncharacterized protein interacts with Dnm1p. Cells disrupted in this new gene, which we call NET2, contain single mitochondrion consists network formed by interconnected...
The HO gene product of Saccharomyces cerevisiae is a site-specific endonuclease that initiates mating type interconversion. We have determined the nucleotide sequence 3,129-base-pair (bp) segment containing HO. contains single long open reading frame encoding polypeptide 586 amino acids, which has unusual (unbiased) codon usage and preceded by 762 bp upstream region. predicted protein basic (16% lysine arginine) calculated to secondary structure 30% helical. corresponding transcript...
The mitochondrial outer membrane protein, Mmm1p, is required for normal shape in yeast. To identify new morphology proteins, we isolated mutations incompatible with the mmm1-1 mutant. One of these mutants, mmm2-1, defective a novel protein. Lack Mmm2p causes defect and loss DNA (mtDNA) nucleoids. Like Mmm1 protein (Aiken Hobbs, A.E., M. Srinivasan, J.M. McCaffery, R.E. Jensen. 2001. J. Cell Biol. 152:401–410.), located dot-like particles on surface, many which are adjacent to mtDNA While...
The mitochondrial inner membrane contains two separate translocons: one required for the translocation of matrix-targeted proteins (the Tim23p-Tim17p complex) and insertion polytopic into Tim54p-Tim22p complex). To identify new members complex, we screened high-copy suppressors temperature-sensitivetim54-1 mutant. We identified a gene,TIM18, that encodes an integral protein membrane. following genetic biochemical observations suggest Tim18 is part complex in membrane: multiple copies TIM18...