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Department of Chemistry & Biochemistry

Florida International University
University Park
11200 SW 8th Street
Miami, Florida 33199

Office: CP 406
Phone: (305) 348-7406
Fax: (305) 348-3772
Email: miksovsk@fiu.edu

Research Projects



i)             Mechanism of signal recognition and transduction in calcium binding proteins.

Neuronal calcium sensor proteins represent a distinct family of EF-hand calcium transducers that are involved in regulation of several aspects of neuronal function. Downstream Regulatory Element Antagonist Modulator (DREAM), also known as calsenilin or potassium channel interacting protein-3 (KChIP-3), is a multifunctional protein that directly controls the activity and assembly of the potassium voltage channel, interacts with presenilin and APP processing, and is responsible for repression of gene transcription by binding to the DRE sequence of DNA. In order to fully understand the most basic aspects of neuronal regulation by Ca2+ ions, we use time resolved photothermal techniques as well as time resolved fluorescence and polarization to monitor time resolved volume and enthalpy changes associated with ligand binding to DREAM protein.

ii) Conformational dynamics in vertebrate hexa-coordinate hemoglobins

Two hexa-coordinate heme proteins have recently been discovered in humans and other vertebrates. Neuroglobin (Ngb) has been found predominantly in brain tissue where it plays important role in the protections of neuronal tissue under conditions of hypoxia and ischemic stress. Cytoglobin (Cygb) is found in connective tissue of body organs such as including lung, heart and brain. Physiological role of this protein has not been fully established, however, several evidences point out to its role in protecting cells against oxidative stress. Cygb was also associated with several types of cancer including sporadic non small cell lung cancer, and head and neck cancer. Our long term goal is to unravel the physiological function of Ngb and to understand the structure-function relationship in the family of hexa-coordinate globins. Our specific goals are i) to determine the time profile and energetic of conformational changes associated with ligand (O2 and CO) binding to Ngb and Cygb and ii) to determine flexibility of the protein structure as a function of the ligand binding to hxHb.

 

iii)            Zeolite-like-metal organic framework as a host system for photochemical processes

 Metal organic frameworks (MOFs) have attracted significant attention due to their elegant topology, relatively straightforward synthesis and potential applications in sensor technology, optoelectronics, chemical separations, gas storage, catalysis etc. In general, MOFS are assembled from modular organic building blocks that are non-covalently linked to a central metal cation. One of the more attractive targets for MOF design are the zeolite-like topologies due to the high versatility of naturally occurring zeolites. Recently, the synthesis of several MOFs with zeolite-like topologies (ZMOF) have been reported using zinc, cadmium, or indium as the metal ion source. Such three dimensional zeolitic networks provide critical advantages for developing new classes of zeolites-like-materials since the cavity dimensions can be ‘tuned’ and functionalized through modification of the organic ligands or through encapsulation of various guest molecules. We focus on functionalization of ZMOF material with common photosensitizers, characterization of photosensitizer – framework interactions and exploring possibility of singlet oxygen generation within the framework.

 

Group Members

 

 

Current group members:

 

Mrs Luisana Austudillo (PhD student ):

Project: Conformational Dynamics Association with Ligand Binding to Six-Coordinated Hemoglobins

 

Publications:

Astudillo L, Bernad S, Derrien V, Sebban P, Miksovska J. “Probing the role of the internal disulfide bond in regulating conformational dynamics in neuroglobin. Biophys J. 2010 Jul 21;99(2):L16-8.

 

Jaroslava Miksovska and Luisana Astudillo (2011). Time Resolved Thermodynamics Associated with Diatomic Ligand Dissociation from Globins, Thermodynamics - Interaction Studies - Solids, Liquids and Gases, Juan Carlos Moreno-Pirajan (Ed.), ISBN: 978-953-307-563-1,

 

Presentations:

Luisana Astudillo, Pierre Sebban, Jaroslava Miksovska, “The Role of the Internal Disulfide Bond in the Conformational Dynamics of Neuroglobin54nd Annual Meeting of Biophysical Society, San Francisco, CA, February 2010.

 

Mr Walter Gonzalez (PhD student ):

Projects: Theromodynamics of Ca2+ association to calcium transducers

 

 

Mr Khoa Pham (MS student)

Project: Signal recognition and transduction in neuronal calcium sensors

 

Presentations:

Khoa Pham, Jaroslava Miksovska, “Conformatinal Dynamics Of Cytochrome c Encapsulated In AOT Reverse Micelles” 53nd Annual Meeting of Biophysical Society, Boston, February 2009.

 

Mr David Butcher (MS student)

Project:

Previous group members:

Miss Simona Horsa (MS student);

Publications:

Miksovska J, Horsa S, Davis MF, Franzen S. Conformational dynamics associated with photodissociation of CO from dehaloperoxidase studied using photoacoustic calorimetry. Biochemistry. 2008 Nov 4;47(44):11510-7.

 

Presentation:

Horsa, S., Perez, K., Miksovska, J. Evaluation of photophyrisal properties of methelen blue incorporated within ZMOF framework. 54nd Annual Meeting of Biophysical Society, San Francisco, CA, February 2010.

 

Simona Horsa, Xiaotang Wang, Jaroslava Miksovska. Structural Dynamics in Chloroperoxidase: A Photoacoustic Study. 54nd Annual Meeting of Biophysical Society, San Francisco, CA, February 2010.

 

Simona Horsa, Xiaotang Wang, Jaroslava Miksovska. Dynamics And Energetics Associated With Ligand Photodissociation From Co Bound Chloroperoxidase. 53nd Annual Meeting of Biophysical Society, Boston, February 2009.

Mr Gangadhar Dhulipala (MS student)

Publication:

Dhulipala G, Rubio M, Michael K, Miksovská J. Thermodynamic profile for urea photo-release from a N-(2-nitrobenzyl) caged urea compound. Photochem Photobiol Sci. 2009 Aug; 8(8):1157-63.

 

Presentations:

Gangadhar Dhulipala, Jaroslava Miksovska, Characterization of Conformational Transitions in Dream Protein using Fluorescence Spectroscopy. 54nd Annual Meeting of Biophysical Society, San Francisco, CA, February 2010.

 

Gangadhar Dhulipala, Jaroslava Miksovska, Characterization Of Ca2+ Photo-release From DM-nitrophen Using Photothermal Beam Deflection. 53nd Annual Meeting of Biophysical Society, Boston, February 2009.

 

Funding

 

Ongoing research support

Florida Department of Healthy, James & Esther King Foundation, “Conformational Dynamics in Hexa-coordinated Hemoglobins”. Role: PI, $ 387,063, July 2010 – June 2013.

 

National Science Foundation, MCB1021831, Conformational Dynamics Associated with Ca2+ binding to DREAM Protein. $ 523, 223, July 2010 – June 2013.

 

Completed Research Support

American Heart Association, Ohio Valley Affiliate, Beginning Grant In Aid; “Thermodynamic Profiles for Calmodulin Signaling.” Role: PI; $130,000, July 2006-June 2009.

 

© 2010