Biomedical Solid-State NMR

PhD & Postdoc positions: ssNMR / quadrupolar nuclei / MD (Antibiotics / Utrecht)

Positions are funded by an ERC Consolidator grant to Markus Weingarth (‘The mechanisms of lipid-targeting antibiotics’).

All projects deal with antibiotics/antibiotic leads for which the molecular mechanisms are unknown. Medical chemistry is done in the dark. These antibiotics are i) either already clinically used or ii) novel drugs from so-called ‘unculturable’ bacteria, isolated by our collaborators. We employ an array of biophysical techniques with ssNMR at the core. Please see our recent work on teixobactin (Shukla et al., Nature 2022) as an example. Our lab hosts strong NMR equipment (e.g., 1200 MHz magnet / 800 MHz DNP), is well-founded, and we collaborate with groups/companies that strive to bring drugs to the clinics.

I. Postdoc position (3 yrs).

Expertise in quadrupolar ssNMR, expertise in DNP/1H-detection is a plus.

Background: Many antibiotics, including clinical used ones, kill bacteria by destroying their cell membranes. This often only works in the presence of specific metal ions (that are quadrupolar & low-gamma). Due to major technical challenges to study ions in complex membrane-settings, how these ions interact with antibiotics is unknown at the molecular level.

The ideal candidate has expertise in quadrupolar* ssNMR and is familiar with DNP-supported and/or 1H-detected ssNMR. Knowledge in biochemistry/molecular biology is not required for the position. Note that we have recently acquired dedicated ssNMR equipment for low-gamma nuclei @ 800 & 1200 MHz (2.5 – 1.3 mm probes). The selected candidate is encouraged to apply for PD fellowships (e.g. MC, EMBO, Frontiers). There’re interfaces with research questions on ion channels.

*you’re also welcome to apply if you have a strong research track record but no knowledge in quadrupolar nuclei

II. PhD positions (2 x)

1. The 1st PhD position deals with MD simulations and structure calculations that are critical for all our projects (see, e.g., Shukla et al., Nature 2022 & Nature Comm 2020). We are especially interested to use computations to study how antibiotics target complex membranes such as outer membranes of Gram-negative bacteria. Some background in bio-computations is required. If desired, the candidate could also combine computations with experimental techniques.
2. The 2nd PhD position deals with experimental mechanistic studies of lipid-targeting antibiotics. The candidate will use a broad spectrum of biophysical (ssNMR, microscopy, calorimetry…) and biochemistry methods. Background in NMR (liquids or solids) is not required (but does not harm); hands-on knowledge in biochemistry/molecular biology is required, knowledge in fluorescence microscopy is a plus. This position will build upon our recent teixobactin paper (Shukla et al., Nature 2022) with a focus on cellular structural biology (especially killing mechanisms against ‘difficult-to-kill-bacteria’).

The Utrecht NMR group hosts strong NMR equipment (10 magnets, including 2 x 700, 800, 900, 1200 MHz magnets, 400/800 MHz DNP, 3.2 – 0.7 mm MAS probes), and dedicated probes for low-gamma nuclei & 19F (for 800 & 1200 MHz).

We have in-house access to modern computer clusters. Wet-labs are well equipped for small molecules. Modern equipment to study drug-receptor interactions is available, and we have access to state-of-the-art microscopy instruments. Furthermore, we have a network of collaborators for techniques like SRM/AFM/cryoET/lipid biochemistry, and particularly for drug discovery (including industrial collaborators). I like point out that PhD students of the group published & graduated in due course, and have won some awards in the recent past (see CV - https://www.weingarth-group.org/group).

Please send your application (including CV) to m.h.weingarth@uu.nl

PD position: please provide two potential reference-contacts; PhD positions: 1 reference-contact. Please do not hesitate to inquire about the positions. I would be very happy to discuss in person at the ICMRBS in Boston.

Selected papers about antibiotics

Medeiros Silva et al, Nature Communications 2018

Shukla, Medeiros-Silva et al., Nature Communications 2020

Shukla et al., Nature 2022

Group homepage: weingarth-group.org

Twitter @MarkusWeingarth

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