Mickey
Kosloff
Welcome to my (Mickey Kosloff's) home page. I am working in the
Arshavsky lab
at the Duke University
Medical Center
in Durham, North Carolina.
My interests are focused on the field of
signal transduction. In particular, I aim to decipher how structure encodes interaction
specificity at the protein-family level.
The model system I study is the interactions of G-proteins with the proteins that turn them "off",
the Regulators of G-protein Signaling (RGSs). These families play central roles in communication
within and between cells and are involved in numerous diseases such as cancer,
hypertension, and schizophrenia; they are therefore important targets for basic and applied research.
To address the question of how specificity is dictated in these large protein families,
I use a multidisciplinary bottom-up approach. I combine experimental assays with computational methods
to identify which individual residues in a set of protein complexes underlie similar interactions,
and which residues contribute to selectivity. My research also addresses how the interactions of
G-proteins and RGSs with membranes can further modulate their function and specificity.
By combining the accuracy of biochemical and biophysical experiments with the mechanistic
insights and scalability of computations, these approaches can be extended to the level of
whole families and eventually to the system level.
Past:
Before coming to Duke I was a post-doctoral fellow in
Barry Honig's Lab
at the
Department of Biochemistry and Molecular Biophysics
at Columbia University in New York.
In the Honig lab I focused on computational approaches to understand how
structure determines function and specificity in particular proteins,
worked on quantifying structural differences and identifying sequence similar,
structure dissimilar proteins in the PDB,
and studied the interactions of G-proteins with membranes.
I participated in the Critical Assessment of Techniques for Protein Structure
Prediction (CASP6)
in 2004 as part of the Honig group effort in that experiment, where our
group came in 5th out of more than 200 participating groups.
I also assisted with the prediction of selected signal transduction
targets in CASP7.
I am very grateful to the Human Frontiers Science Program
(HFSP), for supporting my research
with their long-term postdoctoral fellowship, both in Columbia and in Duke.
An abstract summarizing my goals for this fellowship can be found
here.
More distant past:
I completed my PhD studies (Summa Cum Laude) in the
Department of Biological Chemistry
(Institute of Life Sciences)
at The Hebrew University.
My doctoral advisor was
Zvi Selinger
(a few more details about him (in Hebrew) are in the
EMET Prize website
and the
Israeli Prize website).
The subject of my thesis was
"Modulation on G-protein function as molecular switches".
It involved studying G-proteins on two different but complementing levels:
1) Understanding the catalytic properties of G-proteins and restoring
catalytic activity to mutant, inactive G-proteins.
2) Investigating the membrane anchorage of G-proteins and the regulation of
G-protein translocation in the Drosophila visual transduction cascade.
In the fall of 2000 I spent 3 months in Arieh Warshel's group, using molecular simulation to study enzymatic catalysis in the G-protein Ras.
After submitting my thesis and before coming to New York I worked in
Shy Arkin's lab,
searching for membrane-targeting motifs in signaling proteins and analyzing novel SARS
membrane proteins.
Even more distant past:
I received my B.Sc. in Chemistry (Summa Cum Laude) in the 'Amirim' honor program at The Hebrew University. Beyond that, it's all a blur...
This website is still under construction and parts are still out of date. My apologies.
If you come across any errors or browser-specific problems,
please let me know.
Best viewed in 1024x768 resolution or higher.
[Last (partially) updated - Nov. 2008]
Click for the good stuff
In memory of
