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Austin McHenry

austin_r3.jpg

Education

  • B.S. Biochemistry, University of Michigan-Ann Arbor (expected to graduate in May, 2012)

Selected Awards

  • PPG Undergraduate Chemistry Award, April 2010
  • James E. Harris Scholarship, April 2011
  • University Honors, University of Michigan 

Meeting Presentations

  • McHenry, A., Sciacca, M., J.R. Brender, Hartman, K., Ramamoorthy, A. (2011) The Role of Cholesterol and Membrane Curvature on the IAPP Lipid Bilayer Interaction: The Dynamic Behavior of Chol and PE in Vesicle Systems upon IAPP Incubation. 2011 Biophysical Society Meeting Abstracts. Biophysical Journal, Supplement, 20a, Abstract, 814-Pos.
  • McHenry, A., Ramamoorthy, A. Role of Cholesterol on the Antimicrobial Peptide-Lipid Bilayer Interaction in “Raft-Like” Membranes (2011) 2011 Summer Undergraduate Research Symposium. 5 August. University of Notre Dame, South Bend, IN.
  • McHenry, A., J.R. Brender, Hartman, K., Nanga, R., Ramamoorthy, A. Membrane Cholesterol Reduces Islet Amyloid Polypeptide (IAPP) Cytotoxicity and Aids in Increased Lag Time of Amyloidogenic Fiber Formation. (2010) 2010 Hope College Regional Chemistry REU Symposium. 30 July. 64-Pos.

Publications

  • (Preprint) McHenry, A.; Sciacca, M.; Brender, J. R.; Ramamoorthy, A. (2012) The Role of Cholesterol on the Antimicrobial Peptide-Lipid Bilayer Interaction in “Raft-like” Membranes. 

Research and Work Experience

  • The Role of Cholesterol on the Antimicrobial Peptide-Lipid Bilayer Interaction in “Raft-like” Membranes
    • April 2011-Present
    • University of Michigan Chemistry, Biophysics
    • Under direction of Professor Ramamoorthy
    • Project description: Characterize the interactions of “raft-like” membranes in response to antimicrobial peptide incubations.
    • Specific Experiences: 
      - Show that liposomes containing “raft-like” domains (those compriosed of either a 1:1 or 1:2 mixture of DOPC/DPPC and between 20 to 40 mol% cholesterol) release a remarkable larger amount of encapsulated dye from LUVs than in similar model membranes containing equal mole percentages of cholesterol.
      - Used Circular Dichroisn, Isothermal Titration Calorimetry, Fluorescence, and other spectroscopic techniques to indicate that as a consequence of cholesterol partitioning preferentially to lo domains in model membranes of coexisting ld-lo phases, the ld phase occupies a very suitable domain of relatively small surface area and fast lateral lipid diffusion, both of which allow for increased antimicrobial activity caused by either pore formations or carpet/detergent disturbances.

      AMP-Raft

    Figure: Three distinct membrane systems are presented here: one containing homogenous, fluid, liquid-crystaline lipid (DOPC), another containing homogenous, rigid, gel-phase lipid (DPPC), and another heterogenous mixture of liquid-crystalline and gel phase lipids (DOPC/DPPC).  When cholesterol, a membrane-rigidifying component, is incorporated into each of these systems, one would expect each to become more impregnable against antimicrobial peptide penetration than its originally less rigid counterparts.  One would expect the more rigid membrane (DOPC/DPPC/Chol) to become even more rigid than (DOPC/Chol).  Instead, our research has shown that because membranes containing (DOPC/DPPC/Chol) form discrete phasal domains sometimes referred to as ‘membrane rafts,’ cholesterol partitions more favorably into only one domain, causing the other to become more vulnerable to membrane disruptive peptide attack.  

  • The Role of Cholesterol on the IAPP Lipid Bilayer Interaction
    • April 2010–August 2010
    • University of Michigan Chemistry, Biophysics
    • Under direction of Professor Ramamoorthy
    • Project Description: Elucidate specific cytotoxic peptide-lipid interactions that may lead to novel therapeutic interventions to decrease β-cell death during type II diabetes.
      - Extend previous observations of the importance of lipid composition on the cytotoxic effects of IAPP.
    • Specific Experiences:
      - Show that when not in raft domains, cholesterol stabilizes membranes, preventing IAPP fiber formation and disruption.
      - Show that raft membranes present an area of compromised integrity against IAPP disruption.  Show distinct secondary structure of IAPP in Raft membranes.
  • Membrane Curvature and Lipid-Raft-Microdomain Composition on Islet Amyloid Polypeptide-Induced Membrane Disruption
    • January 2010-April 2010
    • University of Michigan Chemistry, Biophysics
    • Under direction of Professor Ramamoorthy
    • Project description: Characterize the toxicity of IAPP, particularly at near physiological, heterogeneous membrane composition.
      - Better understand the binding mechanisms of IAPP, an amyloid peptide which has been implicated in β- cell death during type II diabetes mellitus (DM2).
    • Specific Experiences:
      - Determine IAPP fiber formation kinetics via fluorescence measurements with BioTek Synergy 2 Multi-Mode Fluorescence Microplate Reader.
      - Determine IAPP membrane disruption by release of encapsulated dye from model liposomes upon incubation.
      - Show that toxic versions of IAPP induce negative curvature, and that negative curvature decreases first phase peptide disruption but enhances that from the second phase.

Memberships

  • Member, Biophysical Society
  • Member, American Chemical Society
  • Member, University of Michigan Society of Biology Students
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