Irina I.
Serysheva, Ph.D.
Department of Molecular Physiology & Biophysics
Baylor College of Medicine
One Baylor Plaza, Houston, TX 77030
Tel.: (713) 798 - 6989
Fax: (713) 798 - 3475
E-mail: irinas@bcm.tmc.edu
Current Position
Assistant Professor (Non Tenured Track)
Department
of Molecular Physiology & Biophysics
Educational
Background
Ph.D., Biochemistry, 1984, A. N. Bach Institute of
Biochemistry, Russian
M.Sc., Biochemistry (specialization: Molecular
Virology), 1978,
B.
S., Biochemistry, 1976, M. V. Lomonosov State University,
Professional
Experience
12/1997 - present, Assistant Professor, Department of
Molecular Physiology and Biophysics, Baylor College of Medicine,
09/1994 – 11/1997, Instructor, Department of
Molecular Physiology and Biophysics, Baylor
10/1992 – 08/1994, Research Associate, Department of
Biochemistry, Baylor
1984 - 1992: Senior Scientist, Senior Research Fellow
, Research Scientist, Postdoctoral Fellow, A. N. Bach Institute of Biochemistry
of Russian Academy of Sciences, Moscow, Russia.
08/1990 - 03/1991, Visiting Scientist at Department
of Molecular Biology and Microbiology, Tufts University, School of Medicine,
Boston, MA (Dr. Edward Goldberg)
02/1990
– 08/1990, Visiting Scientist at Department of Microbiology,
Awards and
Honors
Research Grants from Muscular Dystrophy Association
of
American Heart Association, National Scientist
Development Grant recipient (
Baylor College of Medicine, Junior Faculty Seed Grant
recipient, (1994 – 1996).
A. N. Bach Institute of Biochemistry (
Russian
National Merit Scholarship of
Gold
Medal of the Russian Government upon graduation of high school.
Societies
American Biophysical Society, 1994 - present
Teaching
Experience
·
Instructor of Tutorial
on Electron Cryomicroscopy at National Center for Macromolecular Imaging,
October 18, 2003, Baylor College of Medicine, Houston, TX.
·
Instructor of
International workshop on Molecular Imaging of the Cytoskeletal Protein
Assembly, April 29 - May 3, 1994, Baylor College of Medicine, Houston, TX.
· 1985 - 1990 - design and full responsibility for
laboratory course on basic techniques for bacteriophages including background
lectures on the structure and assembly of T-even phages for fourth year students
(M.Sc. level) in Moscow State University (Department of Biology, Virology
Division).
Other
Professional Activities
·
Member of
Graduate Student’s Advisory Committee (Mariah Baker, SCMB program at Baylor College
of Medicine).
·
Official
opponent for Ph.D. thesis of Prilipov A.G. in D. I. Ivanovsky Institute of
Virology, Academy of Medical Sciences of Russia, 1992 December, Moscow.
·
Member of the
Organizing committee of International Meeting on "Self-organization and
Assembly of Biological Macromolecules", June 1990,
·
Member of Young
Scientist Committee in A. N. Bach Institute of Biochemistry of Russian Academy
of Sciences, Moscow, Russia (1986 - 1989).
·
Organizer of
Conferences for Young Scientists on the Modern Problems of Biochemistry, 1985 (
·
Reviewer for
All-Union Abstract Journal (Molecular Biology/Virology Sections) 1984 - 1990.
Invited Presentations
“Structure of Ca2+ channels revealed by
Electron Cryomicroscopy and Single Particle Image Analysis”,
“Insights into Excitation-Contraction coupling by
electron cryo-microscopy”, invited speaker at the Gordon Research Conference on
Excitation-Contraction Coupling in Muscle,
"Structural Insights into Excitation-Contraction
Coupling by Electron Cryomicroscopy: A Tale of Two Calcium Channels",
invited seminar in the Department of Physiology,
Medicine,
"Gating of the Skeletal
muscle Ca2+ release channel by Electron Cryomicroscopy",
invited seminar in the Department of Molecular Physiology and Biophysics at
"3D structure of the skeletal muscle Ca2+release
channel in open state by electron cryomicroscopy", speaker at the
Conference on "Ion Channel Structures & Function", Yale
University School of Medicine, New Haven, Connecticut, July 16 -18, 1999.
"3-Dimensional structure of the skeletal muscle
Ca2+-release channel activated by Ca2+ and AMP-PCP". Speaker at 17th Annual Meeting
of Biophysical Society, February 1999, Baltimor.
International Forum on Structure and Function of Ion
Channels, (poster presentation);
"Ca2+ induced conformational changes
in the skeletal muscle Ca2+-release channel". Speaker at the
14th International Congress on Electron Microscopy, September 1998,
Gordon Research Conference on Muscle: Excitation -
Contraction Coupling, (poster presentation); 1998, 2000
Gordon Research Conference on Tree-Dimensional
Electron Microscopy of Macromolecules, (poster presentation); 1995
"3-Dimensional structure of the skeletal muscle
Ca2+-release channel in its open and closed states by electron
cryo-microscopy and angular reconstitution". Department of Molecular
Physiology and Biophysics, Baylor
"3-Dimensional structure of
the skeletal muscle Ca2+-release channel in different functional
states". Speaker at 13th
Annual Meeting of Biophysical Society, March 1995,
"Electron cryomicroscopy and angular
reconstitution used to visualize the skeletal muscle calcium release
channel". Protein structure-function meeting. Department of Biochemistry,
"Structure-function relationships in short tail
fibers of phage T4". International Meeting on "Selected aspects
of physico-chemical properties and function of DNA", June 1992,
"Structure and functions of adsorption apparatus
of Bacteriophage T4". Department of Biochemistry and Molecular Biology,
Medical University of South Carolina, Charleston, SC, January 1990.
"Secondary structure of different isomeric forms
of phage T4 sheath protein (gp18)". International Meeting on the
Bacteriophages and Problems of Immunology, June 1984,
Several seminars in various major Universities and
Research Institutes in
Research
interests
Intracellular Ca2+ signaling
is one of the most ancient second messenger pathways in a cell which is of
vital importance in such diverse
physiological functions as muscle contraction, neurotransmitter release,
fertilization, hormone secretion, gene transcription, metabolic regulation and
apoptosis. It is based on the ability of cells to maintain low levels of Ca2+
(~10-7 M) under resting conditions and to create a rapid and transient
increase of Ca2+(~10-6 M) upon the stimulated entry of Ca2+
ions through the plasma membrane (Ca2+ influx) or via activation of
Ca2+ channels present on intracellular Ca2+ stores (Ca2+
release). Key elements for this pathway are Ca2+ pumps and Ca2+
channels on plasma membrane and on internal organelles. The goal of my research
is to understand molecular mechanisms underlying ion transport into and out of
the cell across the surface membrane, or between different intracellular
compartments through structure-functional studies of membrane proteins and the
macromolecular assemblies they form.
In our studies we use electron
cryomicroscopy and computer reconstruction techniques in conjunction with
biochemical, electrophysiological and molecular biological techniques. To date,
electron cryomicroscopy is proving to be one of the most important structural
approaches in cell biological studies. We use 'single particles' approach which
stands for isolated unordered particles with, in principal, identical structure
and relies on analysis of large numbers of electron images of macromolecules
preserved in a layer of vitreous ice.
Recent focus has been on structural
analysis of integral membrane Ca2+ release channels that mediate
ligand-gated release of Ca2+ from intracellular stores: the inositol
1,4,5-trisphosphate-sensitive Ca2+ release channel (InsP3R),
localized in the endoplasmic reticulum, and the ryanodine-sensitive Ca2+
release channel (RyR), the primary Ca2+ channel in muscle cells.
Both channels are large homotetrameric protein complexes with a molecular mass
of ~2.3 MDa for RyRs and 1.2 MDa for InsP3Rs. Large size and dynamic
properties of these ion channels render their structural determination by
standard structural techniques like X-ray crystallography or NMR spectroscopy,
while electron cryomicroscopy is able to tackle both large macromolecular
assemblies as well as molecules in different functional states. Another avenue
of our research is the L-type voltage-gated Ca2+ channels. It has
long been appreciated that in muscle cells, excitation-contraction coupling
results from interactions between plasma membrane voltage-gated L-type Ca2+
channels (dihydropyridine receptors, DHPRs) and RyRs in the sarcoplasmic
reticulum. The skeletal muscle L-type Ca2+ channel (~450 kDa) is a
hetero-oligomeric protein complex composed of five subunits arranged in a
1:1:1:1:1 stoichiometry. Even though the resolution of our current structures
is limited to 14-30 Å, the low -resolution information is often useful for
advancing the understanding of the system particularly when the structural
studies are carried out along with biochemical labeling or modification. Our
ultimate goal is extending these studies to higher resolution (8-10 Å) in order
to build an atomic model of these molecular complexes at well-defined
functional states.
Research Support (during the last three years)
·
Research Grant (PI: Serysheva)
Structure-function correlations within
skeletal muscle L-type Ca2+ channel
The
major goal of this project is to determine the membrane topology of the L-type
Ca2+ channel and to map the interaction sites of with the ryanodine
receptor (Ca2+ release channel) from the skeletal muscle SR.
·
Research Grant
(PI: Serysheva)
Structural analysis of the skeletal muscle dihydropyridine receptor
This project aims to resolve the 3D structure of the
skeletal muscle L-type Ca2+ channel by using electron cryomicroscopy
and computer reconstruction techniques.
· AR444864 (NIH/NIAMS) (Co-PI: Serysheva; PI: S. L. Hamilton)
Molecular
Determinants of E-C coupling (renewed:
The major goals of this project is to correlate the
3D structure of the Ca2+ release channel with its functions and to
elucidate the mechanisms by which mutations in the skeletal muscle Ca2+
release channel produce modulation of channel.
· AR41729 (NIH/NIAMS) (Co-PI: Serysheva; PI: S.
L.Hamilton )
Structural
Analysis of Ca2+ Release Channel
The major goals of this project is to correlate the
3D structure of the Ca2+ release channel with its functions and to
elucidate the mechanisms by which mutations in the skeletal muscle Ca2+
release channel produce modulation of channel.
·
9730258N (SDG,
PI: Serysheva)
American Heart Association
Structural Analysis of Cardiac Ca2+
Release channel in Different Functional States
The major goal of this project is to define the 3D
structure of the Ca2+ release channel from the sarcoplasmic
reticulum of the cardiac muscle.
Pending
Grants
· R01 GM07284 (NIH/NIGMS) (PI: Serysheva)
Structural
analysis of type 1 inositol 1,4,5-trisphosphate
receptor
Peer-Reviewed
Publications
·
Serysheva, I. I., D. J. Bare, S. L. J. Ludtke, C. A. Kettlun, W. Chiu & G. L.
Mignery (2003). Structure of the Type 1 Inositol 1,4,5-trisphosphate Receptor
Revealed by Electron Cryomicroscopy. J. Biol.Chem., 278, 21319-21322.
http://www.jbc.org/cgi/content/full/278/24/21319
·
Baker M. L., I.
I. Serysheva, S. Sencer, Y. Wu, S. L. Ludtke, W. Jiang, S. L. Hamilton & W.
Chiu (2002). The skeletal muscle Ca2+ release channel has an
oxidoreductase-like domain. PNAS, 99, 12155 -12160.
http://www.pnas.org/cgi/content/full/99/19/12155
·
Serysheva,
http://www.pnas.org/cgi/content/full/99/16/10370
·
Pate, P.,
Mocha-Morales, J., Wu, Y., Zhang, J. Z., Rodney, G. G., Serysheva, I. I.,
Williams, B.Y., Anderson, M. E. & S. L. Hamilton (2000). Determinants for
Calmodulin Binding on Voltage-dependent
Ca2+ Channels. J.Biol.Chem, 275, 39786-39782.
http://www.jbc.org/cgi/content/full/275/50/39786
·
Serysheva,
http://www.biophysj.org/cgi/content/full/77/1936
·
Orlova, E.V., I.
I. Serysheva, M. van Heel, S. L. Hamilton & W. Chiu (1996). Two structural
configurations of the skeletal muscle calcium release channel. Nature Struct. Biol.,
3 , 547 - 552.
·
·
Chang, Z., T. P.
Primm, J. Jakana, I. H. Lee, I. I. Serysheva, W. Chiu, H. F. Gilbert & F.
A. Quiocho (1996). Mycobacterium tuberculosis 16-kDa antigen (Hsp 16.3)
functions as oligomeric structure in vitro to supress thermal aggregation. J.Biol.Chem,
271, 7218 - 7223.
http://www.jbc.org/cgi/content/full/271/12/7218
·
Serysheva,
·
Serysheva, I. I.,
Tourkin A. I., Bartish I. V. & Poglazov B. F. (1992). GTP-ase activity of
bacteriophage T4 sheath protein. J.Mol.Biol.,223, 23-25.
·
Serysheva,
·
Serysheva, I. I.,
Venyaminov S. Yu., Tourkin A.I. & Poglazov B. F. (1984). On the presence of
Guanosine phosphate in the tail of bacteriophage T4. J. of Molecular Biology,
179, 565 - 569.
·
Serysheva,
·
Serysheva, I. I.,
Tourkin A. I., Bartish I. V. & Poglazov B. F. (1988). The effect of the
nucleotides on the sedimentation behavior of bacteriophage T4 contracted
sheaths. Doklady Akad.Nauk
·
Gorbatova, L. P.,
Selivanov N. A., Serysheva I. I., Mesyanzhinov V.V. & Poglazov B. F.
(1979). Functional role of baseplate proteins of bacteriophage T4. Doklady
Acad.Nauk
·
Serysheva,
·
Poglazov, B. F.,
Abuladze N. K., Serysheva I. I. & Tourkin A. I. (1988). Application of bifunctional
reagents for studying of the topography of bacteriophage T4 proteins. In New methods
of practical biochemistry. (Russian),
Review
Articles, Book Chapters
·
Susan L.
Hamilton, Irina Serysheva & Gale Strasburg (2000). Calmodulin and
Excitation-Contraction Coupling. NIPS, 15, 281-284.
·
Serysheva, I.
& S.Hamilton (1998). Ryanodine Binding Sites on the skeletal muscle Ca2+
release channel, in The Structure and Function of Ryanodine Receptors, ed. R.
Sitsapesan and A. Williams, J. B. Lippincott Co., Philadelphia, P.A., 95 - 111.
·
Orlova, E. V.,
·
Serysheva,
Abstracts and Proceedings
Serysheva,
Helling, D. B., B. S. Rao V. L. Papineni,
Danila, C., W. Tang, J.-Z. Zhang,
Serysheva, I. I., D. Bare, S. L. Ludtke, C. S.
Kettlun, W. Chiu & G. A. Mignery (2003). 3D structure of the Type 1
Inositol 1,4,5 – trisphosphate Receptor by Electron Cryomicroscopy, Bioph. J.,
84, 281.
Serysheva,
Serysheva,
Serysheva,
Baker, M. L., I. I. Serysheva, Y. Wu, S. Sencer, W.
Tang, P. Pate, J.-Z. Zhang, S. J. Ludtke, W. Jiang, W. Chiu & S. L.
Hamilton (2001). Identification of an N-terminal redox sensor in RyR1. Bioph. J,
80, 330A.
Baldwin, P. R., S. L. Ludtke,
Serysheva, I.I., S. J. Ludtke, S.L. Hamilton
& W. Chiu (2000). Structure of Skeletal Muscle Calcium Release
Channel by Electron Cryomicroscopy: Approaching High Resolution. Bioph. J, 78,
484A.
Serysheva,
Serysheva,
Serysheva, I. I., Orlova E. V., Schatz M., Marks A.,
M. van Heel,
Serysheva, I. I., Orlova E. V., Sherman M. B., M. van
Heel,
Slavik, K. J., Needleman D., Sarkar H., Serysheva I.,
W. Chiu, Marks A., Hamilton S. L. (1995). Interactions of FKBP12 with the Ca2+
Release channel of rabbit skeletal muscle. Bioph. J, 68, A128.
Serysheva,
Serysheva,
Serysheva,
Serysheva,