Faesen, Alex C., Dr.

  • Since August 2017 Max-Planck Research Group Leader, Max Planck Institute for Multidisciplinary Sciences, Göttingen
  • Jan. 2012 – July 2017 Post-doctoral fellow, Max-Planck Institute of Molecular Physiology, Dortmund, Advisor: Prof. Dr. Andrea Musacchio
  • Sept. 2005 to Dec. 2011 Graduate Student, Netherlands Cancer Institute, Amsterdam, Advisor: Prof. Dr. Titia Sixma

Major Research Interests

Spatiotemporal control of protein interactions in signaling pathways is vital in biology. The reversible activation of signaling proteins or complexes through post-translational modifications (PTMs) plays a central role in the regulation of biochemical switches in signal-transducing systems. The primary interest of our research group is in a less studied alternative process in cellular signaling, which is operational in cell division, DNA damage signaling, and autophagy. The signal transduction mechanism relies on the reversible change of a protein’s three-dimensional structure to regulate its protein-protein interaction potential. The crucial paradigm emerging from our previous studies in cell division is that structural conversion of HORMA domains is catalyzed, both at the assembly and the disassembly level, by specialized protein machinery, allowing dynamic control of signaling. We are interested in the molecular mechanisms that regulate the topological changes in these signaling protein complexes, which are essential in the initiation of signaling.

Instead of studying these processes in their complex cellular environment, we aim to biochemically reconstitute these dynamic reactions from purified components in vitro. This allows us to study and manipulate all biochemical activities in great detail, identify the minimal set of components, and ultimately reveal the underlying fundamental principles. Typically, our projects use a bottom-up approach, where we build macromolecular machines from scratch to understand them in details using a combination of biochemical reconstitution, structural biology, and biophysical investigations.

Homepage Department/Research Group


Selected Recent Publications

  • Faesen AC#, Thanasoula M, Maffini S, Breit C, Müller F, van Gerwen S, Bange T, Musacchio A#. “Basis of catalytic assembly of the mitotic checkpoint complex” Nature (2017) Feb 23;542(7642):498-502. doi: 10.1038/nature21384
    # Co-corresponding author
  • Weir JR*, Faesen AC*, Klare K*, Basilico F, Fischböck, Pentakota S, Keller J, Petrovic A, Pesenti M, Vogt D, Wohlgemuth S, Herzog F, Musacchio A. “Insights from biochemical reconstitution into the architecture of human kinetochores” Nature (2016) Aug 31;537(7619):249-253
    * Equal contribution
  • Faesen AC, Luna-Vargas MPA and Sixma TK. “The role of UBL domains in Ubiquitin-Specific Proteases” Biochemical Society Transactions (2012) June 1; 40(3): 539-545
  • Faesen AC*, Luna-Vargas MPA*, Geurink PP, El Oualid F, Clerici M, Ovaa H, Sixma TK. “The differential modulation of USP activity by internal regulatory domains, interactors and seven Ub-chain types”. Chem. Biol (2011) Dec 23; 18(12): 1550-61
    * Equal contribution
  • Faesen AC, Dirac MG, Shanmugham A, Ovaa H, Perrakis A, Sixma TK. “The auto-activation mechanism of USP7/HAUSP by its ubiquitin-like (HUBL) domain is allosterically promoted by GMPS”. Mol Cell. (2011) Oct 7; 44(1): 147-59