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The Berger Lab's research is focused on understanding how multi-subunit assemblies use ATP for overcoming topological challenges within the chromosome and controlling the flow of genetic information. A long-term goal is to develop mechanistic models that explain in atomic level detail how macromolecular machines transduce chemical energy into force and motion, and to determine how cells exploit and control these complexes and their activities for initiating DNA replication, shaping chromosome superstructure and executing myriad other essential nucleic-acid transactions.
Our principal approaches include a blend of structural (X-ray crystallography, single-particle EM, SAXS) and solution biochemical methods to define the architecture, function, evolution and regulation of biological complexes. We also have extensive interests in mechanistic enzymology and the study of small-molecule inhibitors of therapeutic potential, the development of chemical approaches to trapping weak protein/p...rotein and protein/nucleic acid interactions, and in using microfluidics and single-molecule approaches for biochemical investigations of protein dynamics. view more
Mitochondrial dysfunction has long been a consistent observation in Parkinson's disease. To understand the consequences of Parkinson's disease causing genetic mutations on the function of mitochondria, the Bioenergetics Core B will provide the following analyses to the projects in the Udall Center at Johns Hopkins: (1) Measuring rates of respiration, oxygen consumption and ATP generation, (2) Measuring calcium dynamics, (3) Measuring reactive oxygen and reactive nitrogen species, (4) Measuring the activity of the electron transport chain enzymes and metabolic enzymes, and (5) Measuring plasma versus mitochondrial membrane potential and mitochondrial membrane permeability
The MR Research Laboratory focuses on developing and applying nuclear magnetic resonance (NMR) techniques and on measuring energy metabolites and metabolic fluxes with phosphorous (31P) and proton (1H) MRS in patients with ischemia, infarction and heart failure.
Specific studies include: Phosphorus MR studies of myocardial energy metabolism in human heart: We have used spatially localized phosphorus MR spectroscopy (MRS) to noninvasively measure high-energy phosphate metabolites such as ATP (adenosine triphosphate) and phosphocreatine (PCr) in the heart. The PCr/ATP ratio can change during stress-induced ischemia, and a protocol for stress-testing in the MR system has been developed which can detect the changes noninvasively in the anterior wall. Additionally, we've developed methods for noninvasively measuring the creatine kinase (CK) ATP energy supply and used it to measure the CK ATP energy supply in the healthy heart at rest and exercise, in human myocardial infarction, and in ...human heart failure.
Interventional MRI technology: We are developing an RF dosimeter that measures incident-specific absorption rates applied during MRI independent of the scanner and developing MRI-safe internal detectors for higher field use. Outcomes of this research include the "MRI endoscope" that provides real-time, high-resolution views of vessel anatomy and a radiometric approach to detect any local heating associated with the device.
The Pedersen Laboratory is interested in cell energetics and the relationship of cell energetics to molecular medicine and disease. Both mitochondrial and glycolytic processes are being studied at the tissue, cell, and molecular level. Also, the relationship of these processes to cancer and heart disease, the two major causes of death in the U.S., is being studied with the objective of discovering and developing new therapies.
Specific projects in the laboratory that are currently under investigation include: 1) The structure, mechanism, and regulation of the mitochondrial ATP synthase/ATPase complex; 2) The molecular basis of cancer's most common phenotype, i.e., an elevated glucose metabolism; and 3) The regulation of heart function under normal and ischemic conditions as it relates to the mitochondrial ATP synthase/ATPase complex.
Our team consists of chemists, biologists and clinicians who work together in a highly collaborative environment.
Research in the Claypool Lab is focused on defining how lipids and membrane proteins interact to establish and maintain normal mitochondrial function and how derangements in this complex relationship result in pathophysiology. We have demonstrated that yeast lacking tafazzin recapitulates all of the phospholipid abnormalities observed in human patients and many of the mitochondrial defects.
Another major project in our lab focuses on the mitochondrial ADP/ATP carrier that is required for oxidative phosphorylation. Researchers are studying how these novel interactions help establish normal mitochondrial function, the biochemical details of these associations, and whether disturbances in these assemblies can contribute to mitochondrial dysfunction.