Ahmed A. Heikal

Ph.D. Applied Physics, California Institute of Technology, 1995
Associate Professor of Bioengineering

231 Hallowell Bldg.
University Park, PA 16802

Tel: 814-865-8093
Fax: 814-865-0490
Email: aah12@psu.edu
Lab:

Research Interests
The research effort in our Laboratory for Functional Imaging of Biomolecules focuses on understanding complex biological processes on a molecular-level. The following three general themes describe well our research program.

1. Energy Metabolism: Mitochondrion is the power plant that produces most of the energy currencies (ATP) required for the numerous cellular functions. As a result, mitochondrial anomalies are linked to a wide range of health problems that include loss of motor control, muscle weakness, poor growth, cardiac and liver diseases, diabetes, seizures, and neurodegenerative diseases. We are interested in using native biomolecules for studying energy metabolism in cells/tissues as well as for non-invasive cancer diagnostics. Of particular interest to us is investigating mitochondrial anomalies and metabolic activities by exploiting the fluorescence of native biomolecules (e.g., flavin, NADH) that are integral part of the electron transport chain. In addition, we are interested in using these native biomolecules for noninvasive optical diagnostics of tumors. This is because cancer cells have higher energy demands for cell proliferation.



2. Protein-Protein Interaction and Protein Dynamics: Mechanisms and pathways of protein folding have dominated the landscape of experimental and theoretical biophysics for several decades. The reasons are that protein folding plays an important role in numerous biological processes. Recent findings link abnormal protein folding to a wide range of neurodegenerative diseases such as Parkinson's, Alzheimer's and prion diseases. Furthermore, protein-protein interactions and enzyme-catalyzed reactions underlie a vast majority of biological functions in living cells. Our interests in protein studies began with intrinsically fluorescent proteins (IFPs), isolated from jellyfish Aequorea victoria (GFPs) or Discosoma coral (DsRed). In addition to their interesting spectroscopy, dynamics and thermodynamics, the genetic encoding of IFPs allows for site-specific and noninvasive labeling of cells/organs for visualization of gene expression and cellular functions. We are pursuing in-depth understanding of the structure-function relationship in proteins on the single-molecule level.



3. Specialized Domains in Biomembranes: Recent studies link specialized domains “rafts” in plasma membranes to several cellular functions (e.g., signal transduction and intracellular protein trafficking), neurodegenerative diseases (e.g., Alzheimer’s and prion), and virus budding (e.g., HIV). We are interested in a real-time, quantitative investigation of the formation dynamics and functions of these domains. Such quantitative in vivo studies have proven elusive thus far. This is a collaborative effort with Dr. Erin Sheets and her group (Chemistry, PSU), which is a continuation of a recently published work.

To achieve those goals, we are using integrated, noninvasive fluorescence microscopy and spectroscopy techniques with state-of-the-art technologies. We are particularly interested in exploiting the sensitivity of the excited-state dynamics and rotational mobility of biomolecules to (1) their structure, (2) the surrounding environment and (3) the biological state of cells/tissues. Such interdisciplinary research depends on students and postdoctoral associates from different scientific backgrounds such as bioengineering, biology, chemistry and physics.

The cover of the Journal of Biological Chemistry, July 1, 2005 issue, relates to a "paper of the week" article titled "Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy," by H.D. Vishwasrao, A.A. Heikal, K.A. Kasischke and W.W. Webb.

Caption: "Metabolic dynamics in the brain are imaged using the fluorescence of endogenous reduced beta-nicotinamide adenine dinucleotide (NADH). Fluorescence measurements, however, are complicated by the dependence of the quantum efficiency of NADH on its free/bound state. Time-resolved fluorescence anisotropy discriminates free/bound NADH and shows a preferential increase in free NADH during the normoxic (blue curve) to hypoxic (red curve) metabolic transition."

The cover image of the Journal of Physical Chemistry (B), July 15, 2004 issue, relates to an article entitled, “Fluorescence Photo-conversion Kinetics in Novel Green Fluorescent Protein pH Sensors (pHluorins)” by S.T. Hess, A.A. Heikal, and W.W. Webb

Representative Publications

Samuel T. Hess, Ahmed A. Heikal, and Watt W. Webb. Fluorescence Photoconversion Kinetics in Novel Green Fluorescent Protein pH-Sensors (pHluorins). J. Phys. Chem. (B) (2004), In Press.

J. Korlach; D. Baird; A.A. Heikal; K.R. Gee; G.R. Hoffman; W.W. Webb. Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled gamma-phosphate linked GTP analogs. . Proc. Natl. Acad. Sci. U. S. A. (2003), 101(9), 2800-2805.

S.T. Hess; E.D. Sheets; A Wagenknecht-Wiesner; A.A. Heikal. Quantitative analysis of the fluorescence properties of intrinsically fluorescent proteins in living cells. Biophys. J. (2003), 85(4), 2566-2580.

A.A. Heikal; Webb W.W. Multiphoton fluorescence microscopy for functional imaging of biomolecules. Trends in Optics and Photonics (2002), 79 (Nonlinear Optics), 321-323.

S. Huang; A.A. Heikal; W.W. Webb. Two-photon fluorescence spectroscopy and microscopy on NAD(P)H and flavoprotein. Biophys. J. (2002), 82(5), 2811-2825.

A.A. Heikal; S.T. Hess; E.D. Sheets; W.W. Webb. Mutation-photophysics relationship in intrinsically fluorescent proteins. In “Femtochemistry and Femtobiology: Ultrafast dynamics in molecular science”, Editors: A. Douhal and J. Santamaria, World Scientific, Singapore, (2002), Page 774-781.

S.T. Hess; S. Huang; A.A. Heikal; W.W. Webb. Biological and chemical applications of fluorescence correlation spectroscopy: a review. Biochem. (2002), 41(3), 697-705.

A.A. Heikal; S.T. Hess; W.W. Webb. Multiphoton spectroscopy and excited state dynamics of enhanced green fluorescent protein (EGFP): acid-base specificity. Chem. Phys. (2001), 274(1), 37-55.

A.A. Heikal; S.T. Hess; G.S. Baird; R.Y. Tsien; W.W. Webb. Molecular spectroscopy and dynamics of intrinsically fluorescent proteins: coral red (dsRed) and yellow (Citrine). Proc. Natl. Acad. Sci. U. S. A. (2000), 97(22), 11996-12001.

P. Schwille; S. Kummer; A.A. Heikal; W.E. Moerner; W.W. Webb. Fluorescence correlation spectroscopy reveals fast optical excitation-driven intramolecular dynamics of yellow fluorescent proteins. Proc. Natl. Acad. Sci. U. S. A. (2000), 97(1), 151-156.