Open Positions

PhD Position

Fabrication and Characterization of Biocompatible Magnesium Coatings
Institute of Biochemistry, Leipzig University, Annette G. Beck-Sickinger

Metal based implants consisting of titanium, titanium alloys or stainless steel are indispensable for dental and implant medicine. They are used in dental prosthesis and artificial joints as well as stents for widening cardiovascular vessels. Although proven to be effective in numerous applications, these metal implants come with a set of risks, among them immune induced inflammation, encapsulation and rejection. In previous studies, we have developed peptide based coatings of these materials that can minimize these reactions. Another drawback especially of titanium based materials used in bone fractures is that second surgery is necessary for removal after tissue regeneration. As an alternative metal, magnesium is now emerging, which has proven to be biodegradable.

Within the EU M-ERA.NET project “Innovative Strategies for bIoactive/antibacterial advanceD prosthEses (ISIDE)“ coatings are to be developed that enhance the biocompatibility of magnesium and magnesium alloys. Additionally, in order to minimize infections during implant surgery, antimicrobial substances shall be co-immobilized. Peptides will be manufactured by chemical peptide synthesis, proteins will be expressed recombinantly and surfaces will be coated by appropriate techniques. Coatings will be characterized by SEM and their biocompatibility will be examined in cell-based proliferation and viability assays as well as fluorescence microscopy. Together with our cooperation partners, biodegradability will be investigated. In bacterial assays, the antimicrobial activity of the coatings will be explored.

Appropriate candidates are highly motivated team players, but also able to work self-reliantly. They should have a special interest in biomaterials and should be ready to deeply engage into that matter. Experiences in peptide synthesis, protein expression, cell culture and microscopy are welcome, but not mandatory.

The applicants need to hold an M. Sc. degree in chemistry, biochemistry or equivalent. Applications should contain a motivation letter, curriculum vitae, all relevant certificates and degrees as well as contact information of references and be emailed as single PDF to Prof. Dr. Annette Beck-Sickinger. Applications will be reviewed immediately and interviewed (personally/video). Position shall be filled as soon as possible, but preferably before July 1st, 2020.

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PhD Position

Characterizing the molecular interaction between the Y receptors and arrestin
Institute of Biochemistry, Leipzig University, Annette G. Beck-Sickinger

GPCRs initiate pathways of intracellular signal transduction via G-proteins. Subsequently, GPCRs are phosphorylated and bind arrestin. As of now, we have some structure-based understanding of the interaction of GPCRs with G-proteins upon activation. The situation is much less satisfying for the interaction of arrestin with activated GPCRs. Currently, only crystal structures of the rhodopsin/arrestin complex exists determined with the very new femtosecond X-ray laser technology. , Several recent studies have demonstrated that ligand- and G-protein binding result in significant structural polymorphism and dynamic alterations of the individual conformations. It has become clear that the paradigm that GPCR signaling only occurs in response to one unique agonist-based activation is far too simple. The complex dynamic activation of GPCRs can be described by a complex energy landscape that is significantly altered upon ligand and G-protein binding. In contrast to aminergic GPCRs, there is hardly any data available for the conformational dynamics of peptide-binding GPCRs or the alteration of this dynamics due to G-protein or arrestin binding. Therefore, we aim at providing structural data on the active complex of Y receptors with arrestin as well as information on the modification of the equilibrium dynamics of the receptor upon agonist and arrestin binding. To achieve this, we will (i) combine peptide synthesis and protein ligation techniques to prepare NMR-active proteins with a few isolated isotopic labels and EPR-active proteins with introduced spin labels. (ii) We will use solution and solid-state NMR techniques to determine the backbone structure of segments of arrestin in interaction with Y receptors. (iii) We will determine structural constraints to determine the mutual orientation of the Y receptors and arrestin and will verify this with mutagenesis of both, arrestin and two subtypes of the Y receptors (Y1R and Y2R). (iv) The aim of this thesis is to investigate the molecular dynamics of the Y receptors in response to agonist and arrestin binding as well as dynamic alterations in response to conformational changes arrestin undergoes upon binding to the receptor.

Within the just approved CRC 1423 (Structural Dynamics of G-protein coupled Receptors) the project shall be placed and the candidate will work in a stimulatory environment including colleagues from structural biology and molecular modelling. Protein expression and ligation as well as characterization and biological testing will be part of this thesis.

Appropriate candidates are highly motivated team players, but also able to work self-reliantly. They should have a special interest into structural dynamics of G protein-coupled receptors and should be ready to deeply engage into that matter. Experiences in peptide synthesis, protein expression, cell culture and microscopy are welcome, but not mandatory.

The applicants need to hold an M. Sc. degree in chemistry, biochemistry or equivalent. Applications should contain a motivation letter, curriculum vitae, all relevant certificates and degrees as well as contact information of references and be emailed as single PDF to Prof. Dr. Annette Beck-Sickinger. Applications will be reviewed immediately and interviewed (personally/video). Position shall be filled as soon as possible, but preferably before July 1st, 2020.

 

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1Kang Y, et al. Nature. 2015; 523:561-7.
2Zhou XE, et al. Cell. 2017; 170:457-469.e13.
3Manglik A, et al Cell. 2015; 161:1101-11.
4Deupi X, Kobilka BK. Physiology. 2010; 25:293-303.

 

 

 

 

 

letzte Änderung: 16.03.2020