5 Young Researcher/Esr Positions In The Marie Skłodowska Curie Itn “Allostery In Drug Discovery -...

Universities and Institutes of Greece


January 31, 2022


  • Organisation/Company: Biomedical Research Foundation of the Academy of Athens (BRFAA)
  • Research Field: Biological sciences Chemistry Computer science Engineering Pharmacological sciences Physics
  • Researcher Profile: First Stage Researcher (R1) Recognised Researcher (R2) Established Researcher (R3) Leading Researcher (R4)
  • Application Deadline: 31/01/2022 23:59 - Europe/Brussels
  • Location: Greece › ATHENS-Greece, Germany-JÜLICH, Germany-BERLIN, Sweden-STOCKHOLM, France-STRASBOURG
  • Type Of Contract: Other
  • Job Status: Full-time
  • Do you want to participate in a training programme in and beyond the fields of physical chemistry of biological systems, theoretical and computational chemistry, biological chemistry, biochemistry, targeted drug delivery/discovery and medicinal chemistry?

    5 Early Stage Researcher (ESR) positions are available within the EU-funded Marie Skłodowska Curie Innovative Training Network on Allostery in Drug Discovery (ALLODD) under Grant Agreement No. 956314. The ALLODD project is a collaboration between 13 academic and industrial organizations with 14 ESR/PhD students in total. The aim of ALLODD is to train a new generation of scientists to exploit the concept of allostery in drug design, using a whole array of computational and experimental technologies to identify and characterize allosteric modulators of protein function that will be applied to therapeutically relevant systems.

    AVAILABLE POSITIONS ESR 1: Development of a computational methodology to detect allosteric

    pathways in proteins and application in drug discovery

    Host Organisation: Biomedical Research Foundation Academy of Athens (BRFAA), Greece.

    Application: Applicants should apply by email to zcournia">mailto:zcournia@bioacademy.gr">zcournia@bioacademy.gr, indicating Reference: ALLODDESR1.

    Objectives: Characterize protein conformational ensembles (from NMR or clustering MD trajectories) based on their amino acid physicochemical properties, produce features from these properties and select the most discriminant using Linear Discriminant Analysis or Principal Component Analysis, train, test, and validate multiple Machine Learning, Deep Learning, and Ensemble Learning algorithms on proteins with known allosteric pathways in order to classify amino acids that contribute to protein allosteric pathways. Assess the viability of binding sites as allosteric pockets using normal mode analysis or elastic network models. Perform computer-aided drug design in the identified pockets.

    Enrolment in Doctoral degree(s): The ESR will have the possibility to be enrolled in any European University upon mutual agreement.

    Specific Requirements: Applicants must be eligible to work in Greece. Experience with biomolecular simulations, computational chemistry and/or programming skills are desirable. Bachelor's or Master's degree in Chemistry, Physics, Pharmacy, Biochemistry, Engineering, Computer Science, or related field is required.

    Excellent oral and writing skills are required.

    ESR5: Allosteric drugs development for receptor mosaics

    Host Organisation: Forschungszentrum Jülich GMBH (FZJ), Germany.

    Application: Applicants should apply by email to g.rossetti">mailto:g.rossetti@fz-juelich.de">g.rossetti@fz-juelich.de, indicating Reference: ALLODDESR5.


    1) understand receptor mosaics (RMs) allosteric-driven signaling mechanism at the molecular level due to receptor associations and allosteric RM interplay,

    2) develop new multi-target allosteric ligands tailored to pharmacologically relevant RMs.

    Enrolment in Doctoral degree(s): The ESR will be enrolled in the Ph.D. school at the RWTH Aachen.

    ESR6: Structural elucidation of allosteric mechanisms in G-protein

    coupled receptors or other membrane proteins by structural biology methods

    Host Organisation: Charité – Universitaetsmedizin Berlin (Charité), Germany.

    Application: Applicants should apply by email to patrick.scheerer">mailto:patrick.scheerer@charite.de">patrick.scheerer@charite.de, indicating Reference: ALLODDESR6.


    1) Large-scale expression and purification of specific GPCRs (Rhodopsin, MC4R, un-named specific GPCR targets) or other membrane proteins,

    2) Biophysical characterization of allosteric modulator binding to the selected GPCRs targets using Microscale Thermophoresis (MST) or Nano differential scanning fluorimetry (nanoDSF) technologies and Microscale fluorescent thermal stability (CPM) assays or additional cell signaling assays (e.g. nanoBRET),

    3) Structural characterization of the selected receptor-ligand complexes (allosteric ions, modulators, peptides) using protein X-ray crystallography or cryo-EM).

    Enrolment in Doctoral degree(s): No.

    ESR9: Identification of target binding sites using HDX MS and off-

    targets using Proteome Thermo Profiling

    Host Organisation: Karolinska Institutet (KI), Sweden.

    Application: Applicants should apply by email to roman.zubarev">mailto:roman.zubarev@ki.se">roman.zubarev@ki.se, indicating Reference: ALLODDESR9.

    Objectives: A key aspect of the characterization of allosteric sites is their precise localization on the protein target using biophysical methods. In this context, binding-site characterization by differential amide hydrogen/deuterium exchange mass spectrometry (HDX MS) will be used for rapid detection and validation. Although HDX MS has lower spatial resolution (4-8 amino acids) than X-ray crystallography, its speed (≈ 1-2 weeks), low sample consumption (200 nmols) and simplicity (no necessity of protein crystals) makes it an ideal tool for fast binding site confirmation. For each protein, a set of 5 to 10 ligands will be chosen for binding-site characterization. 2) MS methods also provide the key to explore and understand off-target effects (by Proteome Thermo Profiling).

    Enrolment in Doctoral degree(s): The ESR will be enrolled in the Ph.D. school at the Karolinska Institutet (KI).

    More details about the position can be foundhere

    ">https: // www. nature.com/naturecareers/job/doctoral-phd-position-in-struct...

    ESR11: Rational design of positive and negative allosteric modulators of


    Host Organisation: Universite de Strasbourg ( Unistra ), France.

    Application: Applications including a cover letter, a CV, and one or two reference letters should be sent to:

    Marco Cecchini, HDR

    Laboratoire d'Ingenierie des Fonctions Moléculaires

    UMR7177, 4, rue Blaise Pascal, 67000 Strasbourg


    Nicotinic acetylcholine receptors (nAChRs) play a central role in the intercellular communication in the brain and the nervous system and are involved in fundamental processes such as attention, learning, and memory. 1) They are oligomeric protein assemblies that convert a chemical signal into an ion flux through the postsynaptic membrane and their pharmacological modulation is currently developed for the treatment of Alzheimer's, Parkinson's, schizophrenia and depression. 2) Very recently, we proposed a straightforward extension of the popular Monod-Wyman-Changeux (MWC) model for the allosteric transitions of synaptic receptors and found that pharmacological attributes such as potency, efficacy and selectivity of the modulatory ligands can be expressed in terms of the ligand-binding affinity for the active, resting and desensitized states of the receptor. 3) In addition, thanks to the recent improvements in the structural determination of synaptic receptors at high resolution, a number of high-resolution structures of nAChRs in different physiological states and in complex with modulatory ligands (i.e. agonists, antagonists and positive and negative allosteric modulators) have been deposited. 4) Both the recent theoretical and structural advances on the allosteric regulation of synaptic receptors open to a novel paradigm for the identification of neuroactive compounds by modeling and simulations, which we referred to as computational neuropharmacology. 5) In this context, the establishment of accurate and efficient numerical methods for the calculation of conformation-based ligand-binding affinities is essential.

    Objectives: In light of the above, the goals of the project are: (1) Demonstrate that accurate ligand-binding affinity predictions in nAChRs can be obtained using Molecular Dynamics simulations. (2) Provide a proof of principle that potency, efficacy, and selectivity of known nAChR modulators can be accessed from ligand-bin

    Web site for additional job details

    https: // www. nature.com/naturecareers/job/5-young-researcheresr-positions- in-t...

    Offer Requirements Skills/Qualifications


    Contact Information
  • Organisation/Company: Biomedical Research Foundation of the Academy of Athens (BRFAA)
  • Organisation Type: Other
  • Website: https:// www. bioacademy.gr
  • Country: Greece
  • City: ATHENS-Greece, Germany-JÜLICH, Germany-BERLIN, Sweden- STOCKHOLM, France-STRASBOURG