Dr Tobias Wauer
BSc, MSc (Munich), PhD (Cambridge)
Research Fellow (2015)
Originally from Munich I studied Biochemistry as fellow of the German National Academic Foundation (Studienstiftung) at TU München. During my MSc I performed research on DNA Origami (Prof. Hendrik Dietz, TUM) and protein folding (Prof. Ulrich Hartl, MPI Munich). For a year I was also a visiting student at the University of Oxford to work with Prof. Hagan Bayley on new approaches for DNA sequencing using protein nanopores. This is where I grew fond of British people, pubs and College life in particular. In 2011 I started a PhD in Molecular Biology at Cambridge (Trinity College). My PhD research was conducted at the MRC Laboratory of Molecular Biology under the supervision of Dr David Komander and dealt with the molecular origins of Parkinson's Disease. After that I became a Research Fellow at Emmanuel and remained associated with the College ever since. Besides research I am interested in history, traveling, and all sorts of activities associated with mountains.
My research focuses on understanding the molecular mechanism of disease. Insights into how nanometer-sized molecular machines carry out a myriad of tasks inside a cell is not only very interesting, but also provides us with an idea of what to do when there is a molecular malfunction in a state of disease. During my PhD I solved the molecular structure of the protein Parkin. Mutations in Parkin are the most frequent cause for early-onset Parkinson’s disease. Intriguingly, we could map dozens of Parkinson’s disease patient mutations on the structure and for the first time were able to categorize many of them according to their mechanism of action. Moreover, it revealed that Parkin is trapped in an autoinhibited state and requires activation before it can fulfill its protective role in the cell. The race to find the Parkin activator led to the discovery of phosphorylated Ubiquitin. Ubiquitin is a well-established signaling molecule in the cell, but only its phosphorylated form has novel biochemical and structural properties including the propensity to activate Parkin. I subsequently solved the molecular structure of Parkin in complex with phosphorylated Ubiquitin, which revealed the basis of Parkin activation. Insights into processes like these are crucial to eventually identify Parkin activators for the treatment of Parkinson’s disease.
As a Research Fellow at the MRC Laboratory of Molecular Biology I am continuing my work on the role of molecular machines in disease, with a focus on cancer and neurodegeneration.
List of Publications (also Google Scholar Profile):
Mechanism of phospho-ubiquitin-induced PARKIN activation
Wauer T, Simicek M, Schubert A, Komander D
Nature. 2015 July 10, doi:10.1038/nature14879
Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis
Wauer T*, Swatek KN*, Wagstaff JL*, Gladkova C, Pruneda JN, Michel MA, Gersch M, Johnson CM, Freund SM, Komander
EMBO J. 2014 Dec 19; pii: e201489847
The JAMM in the proteasome
Wauer T, Komander D.
Nat Struct Mol Biol. 2014 Apr;21(4):346-8. doi: 10.1038/nsmb.2800.
Lysine 27 ubiquitination of the mitochondrial transport protein miro is dependent on serine 65 of the parkin ubiquitin ligase
Birsa N, Norkett R, Wauer T, Mevissen TE, Wu HC, Foltynie T, Bhatia K, Hirst WD, Komander D, Plun-Favreau H, Kittler JT.
J Biol Chem. 2014 May 23;289(21):14569-82. doi: 10.1074/jbc.M114.563031. Epub 2014 Mar 26.
Construction and manipulation of functional three-dimensional droplet networks.
Wauer T, Gerlach H, Mantri S, Hill J, Bayley H, Sapra KT.
ACS Nano. 2014 Jan 28;8(1):771-9. doi: 10.1021/nn405433y. Epub 2014 Jan 6.
Structure of the human Parkin ligase domain in an autoinhibited state. [COVER]
Wauer T, Komander D.
EMBO J. 2013 Jul 31;32(15):2099-112. doi: 10.1038/emboj.2013.125. Epub 2013 May 31.
OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis.
Mevissen TE, Hospenthal MK, Geurink PP, Elliott PR, Akutsu M, Arnaudo N, Ekkebus R, Kulathu Y, Wauer T, El Oualid F, Freund SM, Ovaa H, Komander D.
Cell. 2013 Jul 3;154(1):169-84. doi: 10.1016/j.cell.2013.05.046.
OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin.
Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D, Hofmann K, Komander D.
Cell. 2013 Jun 6;153(6):1312-26. doi: 10.1016/j.cell.2013.05.014.
A primer to scaffolded DNA origami.
Castro CE, Kilchherr F, Kim DN, Shiao EL, Wauer T, Wortmann P, Bathe M, Dietz H.
Nat Methods. 2011 Mar;8(3):221-9. doi: 10.1038/nmeth.1570.