Objective: Our goal is to advance biomedical research and fundamental discoveries through the development of Flow and Bead Injection technologies and their application to biomedical studies of complex cellular activities, Flow/Bead Injection (F/BI) is a highly adaptive technology that provides full microfluid automation and multiple means of analyses, making it ideally suited for many biomedical research applications. In this proposal, Flow and Bead Injection technologies will be applied to research in aging with a focus on the cellular interactions of reactive oxygen species (ROS) and telomerase kinetics found in cells tissues as elaborated below: ROS Studies: Physiological damage caused by reactive oxygen species (ROS) is an important area of scientific investigation aimed toward understanding this source of cellular damage, with important implication to aging and life span. ROS are known to induce degradations to cellular metabolism and function leading to declines in physiologic function with aging, metabolic disease, apoptosis and neoplastic transformation. However, little is known about the ensuing kinetic events with respect to ROS toxicity and the progression of the cellular aging process. Proposed is the introduction of advanced instrumentation and methods that will allow researchers to examine cellular events in real time and quantify the chemistries of these important biomedical interactions Application of the instruments developed in this project will provide a means of screening antioxidants for their ability to reduce oxidative stress. Telomerase Studies: In the absence of telomerase activity, telomeres shorten and this shortening is thought to be the main determinant of cellular senescence. Conversely, activation of telomerase is found in approximately 90% of cancer cells Telomere shortening has also been correlated to DNA damage and genomic instability, important in the research areas of aging, cancer, and cell. With the advent of telomerase inhibition drugs standard methodology for neoplastic transformation determination do not distinguish the difference between telomerase and telomerase activity. Needed is a novel analytical approach for the study of telomerase and its ramifications to cancer and aging. Proposed methodology will provide a means of screening telomerase inhibitors for their use in cancer treatment.
|Lähdesmäki, Ilkka; Chocholous, Petr; Carroll, Andrea D et al. (2009) Two-parameter monitoring in a lab-on-valve manifold, applied to intracellular H2O2 measurements. Analyst 134:1498-504|
|Lahdesmaki, Ilkka; Park, Young K; Carroll, Andrea D et al. (2007) In-situ monitoring of H2O2 degradation by live cells using voltammetric detection in a lab-on-valve system. Analyst 132:811-7|
|Gutzman, Yan; Carroll, Andrea D; Ruzicka, Jaromir (2006) Bead injection for biomolecular assays: Affinity chromatography enhanced by bead injection spectroscopy. Analyst 131:809-15|
|Ruzicka, Jaromir; Carroll, Andrea D; Lahdesmaki, Ilkka (2006) Immobilization of proteins on agarose beads, monitored in real time by bead injection spectroscopy. Analyst 131:799-808|
|Erxleben, Holger A; Manion, Michael K; Hockenbery, David M et al. (2004) A novel approach for monitoring extracellular acidification rates: based on bead injection spectrophotometry and the lab-on-valve system. Analyst 129:205-12|
|Carroll, Andrea D; Scampavia, Louis; Luo, Dong et al. (2003) Bead injection ELISA for the determination of antibodies implicated in type 1 diabetes mellitus. Analyst 128:1157-62|
|Wu, Chao-Hsiang; Scampavia, Louis; Ruzicka, Jaromir (2003) Micro sequential injection: automated insulin derivatization and separation using a lab-on-valve capillary electrophoresis system. Analyst 128:1123-30|