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Perera Lab: Research Projects and Collaborations

 

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​Dr. ​Rushika Perera
114 AIDL
Microbiology, Immunology, and Pathology
College of Veterinary Medicine and Biomedical Sciences
Colorado State University
Phone: (970) 491-8611
Email: Rushika.Perera@colostate.edu

​Comparative Analysis of Metabolic Requirements for Dengue Virus (DENV) Replication within the Human Host and its Mosquito Vector, Aedes aegypti

This is a ‘Driving Biological Project’ funded by the Virus Pathogen Resource (VIPR), an NIAID biological Resource Center (BRC). The goals are to:

  1. Define the temporal regulation of the metabolome during dengue virus infection in human cells
  2. Profile the metabolome of dengue virus infected Aedes aegypti mosquitoes
  3. Build a DENV-Host/Vector metabolome database available to the scientific community for comparative analyses of common or unique processes perturbed in both the host and vector during virus infection. These efforts will leverage the human and Aedes aegypti genome resources and functional genomics efforts supported by VIPR and VectorBase (VB) and facilitate data linkage between the two BRCs.

Collaborators: Richard J. Kuhn and Catherine A. Hill (Purdue University, West Lafayette, IN)

Metabolic Flux Analyses to Determine how Dengue Virus Reprograms Central Carbon Metabolism in Infected Cells

  • Dr. Jordan Steel (Post-doctoral Fellow) – Perera lab
  • Dr. Jay Kirkwood (Post-doctoral Fellow) – Proteomics and Metabolomics Facility

It is our hypothesis that virus-induced reprogramming of central carbon metabolism (glycolysis and the TCA cycle) drives the observed changes in lipid biosynthesis and membrane architecture in DENV infected cells. This project aims to establish technically advanced mass spectrometry methodology known as “flux analyses” to investigate the role of central carbon metabolism during dengue virus replication in human hepatoma cells. Flux analysis uses stable isotope labeled precursors (ie: 13C-glucose) to monitor the enrichment of the downstream metabolites in a pathway. Thus it provides real time quantitative changes in metabolic pathways during infection. This approach will enable us to reconstruct the metabolic networks taking into account the dynamics of metabolic reprogramming that occurs during DENV infection. To compliment the mass spectrometry analyses we are also using commercially available inhibitors to block certain steps in these pathways and determine their impact on virus replication. This project is funded by the College Research Council (CRC) of Colorado State University (CSU).

Collaborators: Corey Broeckling (Proteomics and Metabolomics Facility)

Investigating the Role of Cellular Lipids During Flavivirus Replication

  • Rebekah Gullberg (Ph.D. Student)
  • Dr. Jordan Steel (Post-doctoral Fellow)
  • Katherine Menning (M.S.-B program graduate)

My laboratory is also interested in the link between membrane rearrangements that occur within infected cells, including the formation of new membranous structures and cellular lipid metabolism. These rearrangements involve enhanced lipid biosynthesis, induced by the expression of virus gene products. Enveloped viruses in general also exploit host-derived lipid membranes to facilitate release from infected cells by budding, and entering cells through an efficient process termed membrane fusion. Our current efforts are aimed at identifying the function of these lipid-mediators and signaling events during virus infection. Since these viruses also replicate within the mosquito and tick vectors, we are also extending these studies to the relevant vectors. The primary goal of this work is to carry out a comparative analysis of the metabolic requirements of mosquito-borne and tick-borne flaviviruses.

Collaborators: Richard J. Kuhn (Purdue University, West Lafayette, IN), Jason M. Mackenzie (University of Melbourne, Australia)

Other Collaborators

Colorado State University:

  • Barry Beaty, Ph.D.; "Metabolomics based discovery of small molecule biomarkers for noninvasive dengue"
  • Sandra Quackenbush, Ph.D.; "CDK8 regulation of dengue virus replication"
  • Corey Bro​eckling​ (Proteomics and Metabolomics Facility); "Metabolic flux analyses to determine how dengue virus reprograms central carbon metabolism in infected cells"

United States

  • Richard J. Kuhn (Purdue University); "Functional Metabolomics of dengue virus infection in the human host and mosquito vector – a novel avenue for antiviral target discovery"
  • Catherine Hill (Purdue University); "Functional Metabolomics of dengue virus infection in the human host and mosquito vector – a novel avenue for antiviral target discovery"
  • Eva Harris (University of California, Berkely); "Metabolomics based discovery of small molecule biomarkers for noninvasive dengue"
  • Aaron Brault (Centers for Disease Control, Fort Collins); "Probing the Impact of Metabolic Perturbations in the Central Nervous System Induced by a Neurovirulent Virus"
  • David John Beckham (University of Colorado, Denver); "Probing the Impact of Metabolic Perturbations in the Central Nervous System Induced by a Neurovirulent Virus”

International

  • Jason M. Mackenzie (University of Melbourne, Australia); "Investigating the role of cellular lipids during flavivirus replication"
  • Cameron Simmons (University of Melbourne, Australia); "Metabolic changes in Aedes aegypti infected with human isolates of dengue virus"
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