Charlotte Softley

Nationality:

  Great Britain

Institution:

Helmholtz Zentrum München

Supervision:

Prof. Michael Sattler (HMGU), Dr. Wolfgang Jahnke (NOVA), Dr. Matteo Gentili (GIO), Dr. Grzegorz Popowicz (HMGU)

Research Topic:

Structural biology and detection of conformational dynamics and transient pockets in protein targets.

About the project:

The aim of my PhD project is to develop techniques for drug discovery using NMR and to make steps towards finding potential leads for development of drugs. My targets will mainly be PEX proteins in T. cruzi, a pathogen responsible for Chagas disease, which is a neglected disease found predominantly in South America. This involves structure determination by NMR, fragment-based drug discovery and work with paramagnetic tags.

I will be using and improving methods to determine/validate the structure of proteins by analysing interatomic (and hopefully intermolecular) interactions from different NMR spectra. I will then screen small fragments using 2D NMR spectra that show specific atom pairs in a molecule, eg hydrogen-nitrogen or hydrogen-carbon, and 1D spectra that show a specific type of atom, eg Fluorine.  These fragments can be combined/grown into complete molecules that fit interesting regions of these proteins. These regions usually help interactions with other molecules in a cell or are relevant in the pathogen’s life cycle, so that disruption causes death, a loss of contagiousness or failure to reproduce.

 

Personal information:

Having grown up in central England and studied in Cambridge, I have now moved to Munich, Germany to carry out my PhD in drug discovery. I love travelling and languages and spend my free time in the mountains, including a lake or river swim in the summer if I can!

 

Secondments:

ETH Zurich (two months), Novartis GmbH (four months), Giotto Biotech (one month)

 

List of publications:

 

List of posters:

Do All Roads Really Lead to Rome? Learnings from Comparative Analysis of Fragment Binding using SPR, NMR, and X-Ray Crystallography. Hassan E, Softley C, Popowicz G, Eriksson PO, Heine A, Sattler M, Klebe G. New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy

Introducing the CSP Analyzer: a Novel Machine Learning-based Application For Automatic Analysis of Bidimensional NMR Data in Fragment-Based NMR Screen. Fino R, Byrne R, Softley C, Sattler M, Schneider G, Popowicz GM. New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy

Design of paramagnetic tags for NMR Spectroscopy: A new strategy to yield fast, selective and irreversible tagging of protein. Denis M, Softley C, Cerofolini L,  Gentili M, Fragai M, Popowicz G, Sattler M, Nativi C, Luchinat C; New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy

Lanthanide binding tags – placing fragments in fast exchange using PCS. Softley C, Denis M, Cerofolini L, Haeussinger D, Ravera E, Fragai M, Luchinat C, Gentili M, Popowicz G, Sattler M; EURO ISMAR, 25 - 30 Aug 2019, Berlin, Germany

Structural analysis of the multidomain protein TIA-1 and its RNA recognition. Martinez-Lumbreras S, Sonntag M, Souza M, Softley C, Sattler M; EURO ISMAR, 25 - 30 Aug 2019, Berlin, Germany

Design of paramagnetic tags for NMR Spectroscopy: A new strategy to yield fast, selective and irreversible tagging of protein. Denis M, Softley C, Cerofolini L,  Gentili M, Fragai M, Popowicz G, Sattler M, Nativi C, Luchinat C; EURO ISMAR, 25 - 30 Aug 2019, Berlin, Germany

Introducing the CSP Analyzer: a Novel Machine Learning-based Application For Automatic Analysis of Bidimensional NMR Data in Fragment-Based NMR Screen. Fino R, Byrne R, Softley C, Sattler M, Schneider G, Popowicz GM. Gordon Research Conference on Computational Aspects of Biomolecular NMR, Jun 9-14 2019, Les Diablerets, Switzerland

Studying protein-ligand interactions using paramagnetic NMR. Softley C; 7th RSC-BMCS Fragment-based Drug Discovery meeting,  March 24 - 26, 2019. Cambridge, UK

Studying PEX14 and ligand binding in solution with the use of paramagnetic DOTA-M8 tag.  Softley C, Denis M, Cerofolini L, Häussinger D, Gentili M, Popowicz G and Sattler M; EMBO Workshop: Challenges for magnetic resonance in life sciences, May 27 - 31, 2018. Grossetto, Italy

Use of Lanthanide Binding Tags in studying PEX14 and ligand binding in solution.Softley C, Denis M, Cerofolini L, Häussinger D, Gentili M, Popowicz G and Sattler M; HDDC 2018, Apr 26/27, Munich, Germany

 

List of presentations:

Placing fragments with lanthanide tags using paramagnetic NMR.
Softley C, Denis M, Cerofolini L, Häussinger D, Gentili M, Popowicz G, Sattler M. New Frontiers in Structure-Based Drug Discovery, Sept. 23-25, 2019, Florence, Italy