Positions available for PhD candidates, postdocs, and research engineers
Our recently funded ERC Synergy Grant “HiSCORE - Highly Informative Drug Screening by Overcoming NMR Restrictions” seeks to advance hyperpolarisation, miniaturisation, parallelisation and spin dynamics, and combine these research themes for highly informative drug discovery by nuclear magnetic resonance. We believe that, eventually, magnetic resonance can provide an in-depth biophysical characterisation of drug candidates in a much shorter time than today, and become a very effective platform for rapid drug discovery.
This highly interdisciplinary project is run by four laboratories (Geoffrey Bodenhausen, Arno Kentgens, Jan Korvink, and Benno Meier) in three institutions (ENS Paris, Radboud University Nijmegen, and Karlsruhe Institute of Technology). Our partners Alvar Gossert (ETH Zürich) and Claudio Dalvit (Trento) complete our team with strong expertise in magnetic resonance (MR) based drug discovery.
We now invite applications from prospective PhD candidates, postdocs and research engineers to join this ambitious research programme. Several positions are available, and we expect frequent and in-depth exchanges between the participating labs. PhD positions will be supervised jointly, and enable one to obtain experience in the participating institutions. The focus of the individual labs, along with open positions, is detailed below.
The ENS lab headed by Bodenhausen will develop methods to improve hyperpolarization by dynamic nuclear polarization (DNP) at low temperatures (ca. 1.2 K), methods to separate stable radicals from analytes in order to extend the lifetimes of hyperpolarized samples, to allow the rapid transport of such samples, etc. The lab is also developing techniques to characterize the interactions between putative drug molecules and their macromolecular targets, to enhance contrast between free and bound molecules, to determine the thermodynamic stability of the drug-target complexes, and to determine the kinetic on- and off rates of the formation of such complexes.
The ENS lab is equipped with an 800 MHz wide-bore (WB) system for MRI, liquids, and solids, with a gyrotron to combine magic angle spinning (MAS) with dynamic nuclear polarization (DNP); a 600 MHz NB system with rapid sample shuttling for relaxometry of longitudinal and transverse relaxation rates, including triple resonance at two fields (14 and 0.33 T); a 400 MHz WB system for solids and liquids, and two polarizers for dissolution DNP, one operating at 6.7 T and the other at 9.4 T, both with cross-polarization at low temperatures, and both connected to either 400 or 800 MHz spectrometers through magnetic tunnels. The lab will soon have a 500 MHz WB system specifically dedicated to the HiSCORE project.
The ENS lab invites applications for open-minded and motivated postdoctoral and doctoral candidates to focus on the following topics:
- Development of new methods to extend the lifetimes of hyperpolarized samples.
- Development of techniques for multiple sample DNP.
- Development of spectroscopic methods, in particular using fluorine-19 NMR, to enhance the contrast between free and bound drug molecules, to determine the thermodynamic stability of drug-target complexes, and to determine the on- and off-rates of the formation of such complexes.
- Interfacing of small chemo-libraries with dynamic nuclear polarization (DNP).
- Development of NMR-based functional assays to optimize enzyme inhibitors.
Application procedure: For more information about these vacancies, please contact: Prof. dr. G. Bodenhausen, email: geoffrey.bodenhausen@ens.fr. Please submit your complete application to Prof. Bodenhausen at ENS lab
The Magnetic Resonance Research Center (MRRC) headed by Kentgens will focus on the development of hyperpolarization methodology in a microfluidic context, including advanced sample handling and use of solvents such as supercritical CO2. We will explore Overhauser DNP, rapid-melt DNP and Para Hydrogen Induced Polarization (PHIP), aiming at a generic approach for hyperpolarizing drug candidates. Further research will include the development of parallel NMR detectors, as well as methods to run experiments independently in each detector.
Our lab is part of the national Dutch NMR facility (uNMR-NL), and houses a range of state-of-the-art spectrometers, including 400, 500 & 600 MHz liquid-state spectrometers, 300, 400, 600 and 850 MHz solid-state NMR spectrometers. The 600 MHz solids machine is equipped with a 396 GHz Gyrotron for DNP. A multipurpose liquids / solids / microimaging 950 MHz spectrometer was installed early 2021. For the HiSCORE project, a dedicated 400 MHz WB spectrometer equipped with a 263 GHz CW oscillator is available. All spectrometers are equipped with a host of commercial and home-built probes. The hyphenation of superfluidic chromatography and NMR has been achieved. The group has unique expertise in the development of miniaturized NMR probe technology.
The MRRC invites applications of PhDs and postdocs with a degree in chemistry or physics. We prefer candidates with a good team spirit, who like to work in an international environment, and are able to collaborate with our partner groups at the crossroads between chemistry, physics, and engineering. In particular, we will focus on the:
- Exploration of PHIP-based protocols as potential polarization sources.
- Development of high-fidelity parallel detectors and probe technology capable of rapid sample shuttling and freeze/melt steps.
- Development of hyperpolarization approaches for simultaneous in-line characterization of multiple samples.
- Development and implementation of hyphenated analysis techniques for pharmaco-metabolomics.
- Application procedure: For more information about this vacancy, please contact: Prof. dr. A.P.M. Kentgens, email: a.kentgens@nmr.ru.nl. You can submit your complete application by clicking one of the following links: Postdoc@RU; PhD@RU
The IMT lab headed by Korvink will develop micro-electro-mechanical-system (MEMS) technologies for parallel NMR signal chains, starting from microfluidics for sample handling, shimmed detector sites, application-specific integrated circuits (CMOS ASICs) for radiofrequency transmission and detection chains, and for NMR signal processing.
The IMT lab is equipped with a 500 MHz WB with liquid, solid, and imaging probes, a small animal 650 MHz horizontal wide bore, a 350 MHz variable field horizontal wide bore; and numerous low field electromagnetic and permanent magnets. In addition, HiSCORE will provide a 150 mm (6”) 3D nanolithography system. IMT has excellent lithography systems available (E-beam, UV projection, UV direct-write, multiple two-photon Nanoscribe systems) and cleanroom processes (ICP, ALD, Sputtering, Electroplating), a fully equipped RF lab, as well as packaging and assembly processes needed for microsystem engineering.
The IMT lab invites applications of enthusiastic, qualified postdoctoral and doctoral candidates, with a university degree in physics or engineering, and with previous experience in one of the following areas: CMOS design, microfluidics, MEMS, and nuclear magnetic resonance hardware design, to focus on one of the following topics:
- CMOS mixed signal design for massively parallel NMR detection chains.
- Massively parallel microfluidic sample handling.
- Massively parallel microfluidic NMR detectors with high spectral resolution.
- Application procedure: For more information about these vacancies, please contact: Prof. Dr. J. Korvink, email: jan.korvink@kit.edu. Please submit your complete application to Prof. Korvink at KIT.
The Meier lab at KIT will develop technologies to scale the supply of hyperpolarized drug candidates. This involves a substantial parallelization of the polarization step, where we target to hyperpolarize 100 sample bullets simultaneously. We will also study DNP mechanisms to reduce the polarization time per sample, and explore DNP mechanisms such as the solid effect that require substantial microwave power. Further research branches are the liquefaction of hyperpolarized solids, and the time-efficient characterization of drug binding.
We are equipped with two 50 mm bore, 9 T polarizers, Bruker 400 MHz NB and WB magnets, a 2 T fast field-cycling system, a state-of-the-art CNC workshop (Haas SMM2, ST10) and a Bezerra Mitika Top.
Our lab invites applications for two post-doctoral researchers, two PhD students and one research engineer:
- Optimization of parallel hyperpolarization with strong microwave fields.
- Development of rapid distribution of hyperpolarized material across many parallel NMR detectors.
- Control of relaxation and thermal mixing during the transfer of hyperpolarized materials.
- High throughput MR-based detection and characterization of ligand binding
- A fixed-term research engineer position to support the laboratory and the construction of new equipment is available for three years.
In addition:
- A joint PhD position with a focus on accelerating sample preparation and characterization of ligand binding is available with Alvar Gossert at ETH.
- Application procedure: For more information about these vacancies, please contact: Dr. B. Meier, email: benno.meier@kit.edu Please submit your complete application to Dr. Meier at KIT.
Prof. Dr. A.P.M. Kentgens,
Magnetic Resonance Research Center,
Institute for Molecules and Materials,
Radboud University Nijmegen,
Heyendaalsweg 135, 6525 AJ Nijmegen, The Netherlands.
Huygens Building Room HG03.343
Tel. +31-24-3652078 / 3652678
e-mail: A.Kentgens@nmr.ru.nl
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