BIOPHYSICAL SOCIETY NEWSLETTER
4
NOVEMBER
2014
Know the Editors
Jane Dyson
Scripps Research Institute
Editor for the Proteins and
Nucleic Acids Section
Q:
What is your area of research?
My lab is interested in proteins as self-assembling
molecular machines. Many, if not all, proteins
will fold into their three-dimensional structures
spontaneously: the information that specifies
the final folded state is present in the amino acid
sequence. We have done a number of experi-
ments to determine how the sequence codes
for folding, using techniques such as nuclear
magnetic resonance (NMR), circular dichro-
ism (CD), and fluorescence spectroscopy. Rapid
mixing techniques allow us to tease out the steps
that occur as a protein folds and to identify the
types of amino acids that participate in the initial
and later steps of the folding process. Proteins are
also versatile and flexible machines, particularly
those proteins that we term “intrinsically disor-
dered” (IDPs). The signature of an IDP is that
it is not folded into a defined three-dimensional
structure, but is nevertheless functional. Many
IDPs need to be disordered in order to perform
their functions, for example, in binding to many
different partners (protein or nucleic acid) in the
cell. Many important cellular systems contain
protein elements that are disordered, and we are
beginning to see how this disorder allows the
system to function as a molecular machine. The
motions of protein chains and their connection
with function, for example, in enzymatic reac-
tions, is another major effort in the laboratory.
Protein dynamics can be measured using NMR
experiments such as relaxation dispersion, which
gives information on the rates of interconver-
sion between states, as well as insights into the
population and structure of alternative (invisible)
states that are frequently intimately connected
with the mechanisms of enzyme catalysis.
Ashok Deniz
Scripps Research Institute
Editor for the Proteins and
Nucleic Acids Section
Q:
What is your area of research?
Research at my lab currently focuses on gaining
a mechanistic understanding of the physics of
protein disorder and complexity, by developing
and using cutting-edge tools of single-molecule
biophysics. Protein disorder and other complexi-
ties are now recognized as integral and function-
ally critical components of the biology of the
cell. Disordered proteins, however, are dynamic,
and exhibit complicated structural and interac-
tion biophysics, which makes them difficult to
study by conventional tools that typically average
information over millions or billions of mol-
ecules, thus washing out important information.
To avoid this loss of information, we develop
and utilize sensitive fluorescence methods that
allow us to examine individual molecules. More
recently, we have also integrated strengths of
novel microfluidic techniques to enhance our
experimental capabilities. This powerful set of
tools has allowed us to uncover critical new
insight, including that (1) some disordered pro-
teins populate compact yet rapidly fluctuating
structures, (2) interactions can exert fine control
over complex, multistate folding-binding energy
landscapes, and (3) differential accessibility of
disordered protein sequence regions can result
in dramatic tunability of binding cooperativity,
and consequently cellular function. Our work
also lends fundamental insight into aspects of
the molecular biophysics of health, for example,
in the context of protein misfolding linked to
Parkinson’s disease. Overall, our research com-
bines insights and tools of physics, chemistry,
and biology, and our developed methodologies
can be used broadly to investigate functionally
important molecular complexity in biology.
Biophysical Journal Corner
Jane Dyson
Ashok Deniz
