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Netherlands : PhD position for the project Illuminating Biophotonic Switches

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The Department of Physics and Astronomy and Laser Centre at VU University Amsterdam has an PhD position for the project Illuminating Biophotonic Switches funded by the Netherlands Organization for Scientific Research (NWO) through the Council for Chemical Sciences (CW) For 1.0 fte

Vacancy number: 1.2010.00163

The Faculty of Sciences consists of four departments; Physics and Astronomy, Informatics, Mathematics and Chemistry and Pharmaceutical Sciences with 600 employees including researchers, lecturers, full- and part-time professors. The faculty offers 10 bachelor and 12 master courses and has over 1600 students

Project description: Illuminating Biophotonic Switches
Biological photoreceptors are exceptionally interesting objects of study, not only in relation to their biological function but also because they can be triggered by a short flash of light, allowing the study of functional protein dynamics over a wide span of timescales. In an important new development, biological photoreceptors have been engineered for use as photonic switches and sensors in cells and tissues. They have a modular architecture with conserved ‘input’ and ‘output’ domains, which can be swapped so that an effector domain with desired properties can be rendered lightsensitive. As the light-absorbing chromophore often is a naturally occurring cofactor in cells (such as flavins or biliverdin), photoreceptor proteins can readily be genetically encoded. The light activation mechanisms of biological photoreceptors are therefore of considerable significance for biomedical technology. Thus, biological photoreceptors represent true biological photonic material, tailored for efficient optical switching through natural selection and amenable to engineering through their modular architecture.

To understand the complex relation between photon absorption and the resulting dynamics that characterize the photoswitched function, the structural changes upon light activation need to be determined. Here, we propose to conduct a comprehensive study of a new type of flavin-binding photoreceptor: the BLUF domain. We aim to resolve its photochemical reaction mechanism, how this mechanism alters the local structure around the flavin cofactor, how this local structural perturbation is transmitted to the molecular surface and in what way the molecular surface is affected. To this end, we will employ novel, state-of-the-art time-resolved vibrational techniques to determine the functional-structural changes and their associated timescales that make the BLUF photoreceptor work, and thus understand its photoswitched function at the molecular level. Importantly, we will use BLUF domains with isotopically labeled flavin chromophores, as well as isotopically labeled amino acids incorporated at critical ‘hot spots’ in the protein. The unique combination of isotopically labeled flavin and amino acids, and time-resolved vibrational spectroscopy will enable unambiguous assignment of transient local structure, in space and in time.

We will assess the photochemical reaction mechanism and resulting local structural perturbations with ultrafast vibrational spectroscopy, in particular femtosecond stimulated Raman spectroscopy (FSRS) and ultrafast infrared spectroscopy. The ensuing stages of the light-triggered chain of structural dynamics, i.e. the signal propagation to the molecular surface and alterations of the molecular surface of the BLUF receptor that enable the signaling function will be assessed by nanosecond to millisecond time-resolved FTIR spectroscopy., i.e. ‘step-scan’ and ‘rapid scan’ FTIR spectroscopy.

For sample material, isotope labeling and molecular biology of BLUF domains, a long-term collaboration exists with Peter Hegemann from Humboldt University, Berlin. Intensive interaction will exist with Bernd Ensing from the Van ‘t Hoff Institute of the University of Amsterdam, who has received a CW-VIDI personal grant on advanced computational chemistry and molecular dynamics simulation of BLUF proteins. This powerful multidisciplinary approach will enable a thorough understanding of the photoswitched function of BLUF domains and the resulting insights may form a basis for rational engineering of biophotonic switches.

Requirements
We are looking for a candidate with a M.Sc. degree in physics, physical chemistry or biophysics. Experience with optical spectroscopy is desirable, but not strictly required.

Further particulars
The appointment will be fulltime for an initial duration of 12 months. After satisfactory evaluation of the initial appointment it will be extended for a total duration of 4 years. You can find information about our excellent fringe benefits of employment at www.workingatvu.nl

Salary
The salary will be in accordance with university regulations for academic personnel, and range from € 2.042,- gross per month in the first year up to € 2.612,- gross per month in the fourth year, based on a fulltime employment.

Information
For additional information please contact: Dr. John Kennis, www.nat.vu.nl/~john
Phone number +31 (0)20 5987212
E-mail: john@nat.vu.nl

Application
Applicants are requested to write a letter in which they describe their abilities and motivation, accompanied by a curriculum vitae and one or two references. Written applications should be sent before September 15th 2010 to:

VU University Amsterdam
Faculty of Sciences
Attn.: Dr. John Kennis
De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands

It is also possible to apply by e-mail to: John Kennis, john@nat.vu.nl
Please mention the vacancy number in the e-mail header or at the top of your letter and on the envelope.

Application Deadline : 15 September 2010

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Posted on 2010-07-11 06:15:43

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