How do ions permeate through membranes?
Research
Living cells and their intracellular organelles are
protected from the environment by membranes: lipid bilayers. For
a large part these bilayers serve as a capacitor to maintain
ionic gradients that are utilized for cellular
signalling. Experimental permeability measurements on pure lipid
bilayers reveal that passive ion leakage does occur, with
anomalous rate differences between protons, other cations, and
anions. Atomistic simulations have the potential to give a
microscopic picture of the yet unknown ion transfer mechanisms
through lipid bilayers. Such a picture will explain the
anomalous rate differences seen in experiments and provide key
insights in the way nature evolved effective barriers against
ion leakage by, e.g., molecular inclusions like sterols. A
potential future application in medicine is the absorption and
transfer of larger charged species (drugs). On a broader
horizon, as a solution to the famous ‘reaction-coordinate
problem’ this study will be the first step for many other rare
processes in complex (biophysical) systems. For more background
see e.g. H.L. Tepper and G.A. Voth, Biophys.J. 88, 3095-3108
(2005), and P.G. Bolhuis et al., Annu.Rev.Chem.Phys. 53 291-318
(2002).
Job description
The candidate will get familiar with and further develop rare
event techniques for application to complex biological
systems. The main focus will be to obtain the global mechanism
for an ion spontaneously crossing a lipid bilayer, in terms of
a number of relevant order parameters. Special attention will
be given to the role of membrane fluctuations and solvent
coordinates in this process. Eventually the research should
lead to the free energy barrier height and rate constant for
the permeability of different ions and membrane widths, and a
unified theory or model that can capture the full range of
available experimental data. The candidate is expected to
actively participate in the group and to present his/her
results at international conferences as well as to publish them
in peer-reviewed scientific journals.
Location
The candidate will work in the Computational Chemistry and
Physics group in the van ‘t Hoff institute for Molecular
Sciences at the UvA, under supervision of
dr. P.G. Bolhuis. During the project there will also be ample
opportunity to interact with the experimental biophysics groups
at AMOLF. Requirements We are looking for an enthusiastic
candidate with a master’s degree in physics or chemistry and an
interest in biophysics. Knowledge of statistical mechanics and
thermodynamics is preferred. Since the work will involve using
and modifying complex simulation codes, good programming skills
(in C and/or Fortran) are required.
Conditions of Employment
When fulfilling a PhD position at the FOM foundation, you will
get the status of junior scientist. You will have an employee
status and can participate in all the employee benefits FOM
offers. You will get a contract for 4 years. Your salary will be
up to a maximum of 2,457 euro gross per month. You are supposed
to have a thesis finished at the end of your four year term with
FOM. A training programme is part of the agreement. You and
your supervisor will make up a plan for the additional education
and supervising that you specifically need. This plan also
defines which teaching activities you will be responsible (up to
a maximum of 10% of your time). The conditions of employment of
the FOM-foundation are laid down in the Collective Labour
Agreement for Research Centres (CAO-Onderzoekinstellingen), more
exclusive information is available at this website under
Personeelsinformatie (in Dutch) or under
Personnel (in English). General information about working
at FOM can be found in the English part of this website under
Personnel. The
'FOM-sollicitatiecode' (in Dutch) applies to this position.
Contact
For more information please contact Dr. P.G. Bolhuis:
bolhuis@science.uva.nl / +31-20-525-6447
Website
http://molsim.chem.uva.nl
Applications You can send your application to:
prof.dr. P.G. Bolhuis Computational Physics and Chemistry van
't Hoff Institute for Molecular Sciences University of
Amsterdam Nieuwe Achtergracht 166 1018 WV Amsterdam, The
Netherlands
Closing time
15 december 2008