Life depends on manipulating metabolic efficiency
by: Nicole Buan
Please see the below link to Professor Nicole Buan's YouTube feed of her MicroSeminar.
The TelePathy Project
Telecommunication Systems Modeling and Engineering of Cell Communication Pathways
Dr. Massimiliano Pierobon and Dr. Nicole Buan, assistant professors in the departments of Computer Science and Engineering and Biochemistry, respectively, have recently received support through the Early-concept Grants for Exploratory Research (EAGER) mechanism by the National Science Foundation (NSF), funded by the Directorate of Biological Sciences, with the participation of the Directorate of Computer & Information Science & Engineering. Through their collaborative project, entitled “TelePathy: Telecommunication Systems Modeling and Engineering of Cell Communication Pathways,” they will explore the application of telecommunications systems engineering to the quantitative modeling of information exchange among biological cells, and the design of techniques able to leverage these pathways for the realization of artificial communication systems.
Professors Pierobon and Buan discovered their shared research interests during the CIBC planning activities during Fall 2013 and consolidated their ideas in the EAGER proposal. Learn more about their NSF award.
Metabolic Investigations of Molecular Mechanisms Associated with Parkinson's Disease
1st International Electronic Conference on MetabolomicsRobert Powers Shulei Lei, Annadurai Anandhan, Ronald L Cerny, Eric D Dodds, Aracely Garcia-Garcia, Reilly Grealish, Yuting Huang, Oleh Khalimonchuk, Roman Levytskyy, Jiahui Li, Nandakumar Madayiputhiya, Renu Nandakumar, Mihalis I Panayiotidis, Aglaia Pappa, Robert C Stanton, Laura Zavala- Flores, Rodrigo FrancoView this presentation here.
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by fibrillar cytoplasmic aggregates of α-synuclein (i.e., Lewy bodies [LB]) and the associated loss of dopaminergic cells in the substantia nigra. But, mutations in genes such as α-synuclein (SNCA) account for only 10% of PD occurrences. The exposure to environmental toxicants including pesticides (e.g. paraquat [PQ]) and manganese (Mn), are also recognized as important PD risk factors. Thus, aging, genetic alterations and environmental factors all contribute to the etiology of PD. In fact, both genetic and environmental factors are thought to interact in the promotion of idiopathic PD, but the mechanisms involved are still unclear. In this study, we report a toxic synergistic effect between α-synuclein and either paraquat or Mn treatment. We identified an essential role for central carbon (glucose) metabolism in dopaminergic cell death induced by paraquat or Mn treatment that is enhanced by the overexpression of α-synuclein. PQ “hijacks” the pentose phosphate pathway (PPP) to increase NADPH reducing equivalents and stimulate paraquat redox cycling, oxidative stress, and cell death. PQ also stimulated an increase in glucose uptake, the translocation of glucose transporters to the plasma membrane, and AMPK activation. The overexpression of α-synuclein further stimulated an increase in glucose uptake and AMPK activity,but impaired glucose metabolism. In effect, α-synuclein activity directs additional carbon to the PPP to supply paraquat redox cycling. Alternatively, Mn induces an upregulation in glycolysis and the malate-aspartate shuttle to compensate for energy depletion due to Mn toxicity. Mn treatment causes a decrease in carbon flow through the TCA cycle and a disruption in pyruvate metabolism, which are consistent with a dysfunctional mitochondria and inhibition of pyruvate dehydrogenase. The overexpression of α-synuclein was shown to potentiate Mn toxicity by glycolysis impairment by inhibiting aldolase activity. In effect, α-synuclein overexpression negates the metabolic response to alleviate Mn toxicity that results in an increase in cell death.