PhD student profiles

     
     
   
Felix Schumacher

Michal Koenner
Michal joined the ISMB's Wellcome Trust 4-year Interdisciplinary PhD Programme in Autumn 2010.

Project title
Structural studies of bacterial Type IV secretion systems

Principal investigator: Professor Gabriel Waksman, ISMB, Department of Biological Sciences (Birkbeck) and the Department of Structural and Molecular Biology (UCL)
Co-investigators: Professor Helen Saibil, Department of Biological Sciences, Birkbeck

 
Background

2010: Senior Honours research project
Purification and crystallisation trials of a soluble STAS domain of a bacterial sulfate transporter SulP
University of St Andrews
Supervisor: Professor Jim Naismith

Summer 2009: Wellcome Trust Biomedical Scholarship
Supervisor: Dr Ulrich Schwarz-Linek, Centre for Biomolecular Sciences

I spent 8 weeks investigating the structure and the presence of a rare isopeptide crosslink in a CnaB2 domain of the fibronectin binding surface protein FbaB from S. pyogenes. I used standard recombinant protein expression procedures, automated Ni-NTA purification, multidimensional NMR, mass and CD spectroscopy, as well as thermal-shift fluorescence. Gained experience with using NMR software.

Abbott Laboratories GmbH & Co. KG, Wiesbaden, Germany
Rare Reagents Team Intern.
3 weeks assisting in manufacturing and quality testing laboratories in the Diagnostics division. The techniques used include purification of recombinant antigens, ammonium sulfate precipitation of antibodies, Dot Blott and buffer preparations.

Summer 2008: Research Intern, University of St Andrews
Supervisor: Prof. Jim Naismith, Centre for Biomolecular Sciences
I spent 7 weeks working on recombinant expression, purification and kinetic studies on single-point site-directed mutants of the AcsD enzyme (a bacterial NIS siderophore synthetase)

 
Rotations

Rotation1
Supervisor: Dr. Maya Topf, Birkbeck
Project: Integrative computational modelling of a type IV secretion system.
Aim: To integrate all available structural and functional peces of data about the type IV secretion machinery to produce its structural model.
Techniques learned:

  • Basic bioinformatics, such as fold recognition, homology modelling, threading, structural classifications.
  • Python programming language
  • Database design in MySQL
  • PostScript programming

Rotation 2
Supervisor: Dr Alethea Tabor
Project: Semisynthesis of bifunctional inhibitors of a HP0525 ATPase.
Project aim: To design and produce bifunctional (peptide-small molecule) bioconjugates as inhibitors of HP0525 – a cytoplasmic, membrane-associated Helicobacter pylori Type IV secretion ATPase.
Techniques used:

  • F-moc solid phase peptide synthesis
  • Native chemical ligation
  • Expressed protein ligation
  • Protein purification

Rotation 3
Supervisors: Professor Gabriel Waksman, Professor Helen Saibil
Beginning of my current PhD project

 

PhD project
Secretion is the passage of chemicals and macromolecules across cellular membranes central to all life. Most pathogenic microorganisms use specialised cell-envelope embedded secretion systems, classified into six different types (I-VI). Of these, type IV secretion systems (T4SSs) are particularly versatile, complex and critical from a medical point of view, since many self-transmissible T4SS-encoding plasmids also confer antibiotic resistance. Structural and functional studies of T4SSs have been hampered by their inherent instability and low-abundance in cells. Yet, full structural characterization of the complex is critical for understanding its mechanistic details, which would then guide design of its suitable selective inhibitors and shed light on bacterial gene transfer. To date, our lab has managed to solve an electron-microscopy structure of a 1.1 MDa central core complex of a T4SS. My PhD research is aimed at isolating and imaging of bigger T4 subassemblies using various modern structural techniques.

ISMB, with its rich research diversity is uniquely suited for students on the inherently interdisciplinary Wellcome Trust PhD Programme. Ever since commencing my PhD work, I’ve been exposed to an unprecedented variety of new techniques in very different areas, ranging from electron microscopy, through protein semisynthesis to computational database design and programming. The very well structured, yet flexible nature of the programme has allowed me to take the full advantage of opportunities for interesting collaborations, hence opening up the access to more state-of-the-art research facilities.

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