Event Details

From April 09, 2021 09:00AM
To April 09, 2021 07:00PM

April 9. 2021 at 10:00 a.m


Invited speakers:

Julien Orts (ETH Zürich): Protein-ligand complex binding pocket structure determination with NMR, the NMR Molecular Replacement method

Here, we present NMR2 (NMR Molecular Replacement), a MR-like approach in NMR to determine the structures of the binding pockets of ligands at atomic resolution. The calculation of structures of protein-ligand complexes relies on the collection of unassigned semi-quantitative inter-molecular NOE distance restraints and on previously solved structures.[1] The NMR2 method uses a high throughput structure calculation protocol, rather than a docking-scoring simulation. It is fast since it requires only a few days of measuring time and bypasses the time-consuming sequential assignment steps for the protein.
We will present multiple NMR2 applications covering several ligand topologies ranging from peptidomimetic to small molecules that bind strongly or weakly to protein receptors. We also report how NMR2 can make use of partially labelled protein using methyl-specific isotope labelling. Our findings demonstrate that NMR2 may open an avenue for the fast and robust determination of the binding pocket structure of ligand-protein complexes at atomic resolution.

E. Yvonne Jones (University of Oxford) : From structure to mechanism in the assembly and modulation of cell surface signalling complexes

In my laboratory we combine x-ray crystallographic analyses with biophysical, electron and light microscopy based approaches to study the assembly and modulation of cell surface signalling complexes involved in development and tissue homeostasis. We aim to generate mechanistic insights, at atomic resolution, which can be tested by functional studies in vitro and in vivo. I will discuss some of the recent results we have generated by applying this approach to the signalling mechanism of the semaphorin-plexin cell guidance system and to the extracellular modulation of signalling by the morphogen Wnt.

Ervin Welker (ELKH TTK) : Nucleases of the CRISPR system, their function and applications

From the 1950s onwards, with the knowledge of the structure of DNA and the methods developed to rewrite it, a scientific development began that is still proceeding at a tremendous pace. One, if not the most significant milestone, was the discovery of the CRISPR / Cas system and its use as an effective genome-modifying tool that has led to explosive advances in molecular biology and related sciences. The most commonly used proteins of the CRISPR system are the Cas9 and Cas12a orthologs, the single-polypeptide RNA-guided nucleases of the type 5 system. With the help of these nucleases, we can create and perform relatively random deletions, insertions, or any type of changes with base pair precision by using donor DNA at a given, predetermined site in the genome. Nickase and inactive variants of the nucleases and proteins with specific functions that are fused to them can perform transcriptional activation and inhibition of selected genes, and introduce point mutations and minor deletions and insertions with base pair precision without the use of donor DNA. In order to use nucleases and their variants as efficiently as possible, significant progress has been made in understanding their mechanism of action and in increasing their efficiency, specificity, and the range of sequences that can be targeted.

Noémi Lukács (SCICONS, Szirák) : Insights into the world of dsRNAs and vaccines from the perspective of dsRNA-specific antibodies

In my presentation, I will present the biochemical and specificity characterization of double-stranded RNA-specific antibodies, and give an insight into the role of dsRNAs in viral infections, using the example of SARS-CoV2, detailing the types of studies used by Cov research on our antibodies. In addition, I will talk about the exciting new areas of research that the role of dsRNAs in the immune response has opened up, which has contributed to the development of mRNA vaccines, among other things, but also plays a role in cancer research or the biology of aging. GINOP-2.1.7-15-2016-01586

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