Beat Fierz studied Biophysical Chemistry in the University of Basel at the Biozentrum. There, he also performed his PhD studies (2002-2006) with Prof. Thomas Kiefhaber, investigating the dynamics of synthetic polypeptides and protein secondary structure elements using ultrafast time-resolved spectroscopy. In 2007 he joined the laboratory of Prof. Tom W Muir at the Rockefeller University, New York, and later Princeton University, New Jersey, developing chemical biology approaches to reveal chromatin structure formation depending on histone post-translational modifications. In 2012, Beat Fierz was appointed Tenure Track Assistant Professor for the newly created Chaire Fondation Sandoz en chimie biophysique des macromolecules (LCBM) at ISIC, and promoted to associate professor in 2019. The research of his laboratory focuses on the study of the structure, dynamics and function of chromatin and related multi-protein complexes in vitro and in cells. These investigations require an interdisciplinary approach at the interface of chemistry, biology and biophysics.
About his talk: Semisynthesis to dissect dynamic protein regulation by post-translational modifications
Post-translational modifications (PTMs) of proteins are critical for the regulation of many cellular processes, including in genome organization via chromatin or in the cytoskeleton, in particular in the regulation of the microtubule network. We are combining chemical biology approaches and mechanistic biophysics to understand PTM signaling in these systems.
Ubiquitylation of histone proteins plays an important role in many processes, including gene activation, repression and DNA damage repair. We have a long-standing interest in dissecting the diverse and context sensitive-roles of this intriguing PTM, the mechanisms of its installation and consequences of downstream signaling. To this end we develop methods to synthesize ubiquitylated chromatin fibers and dissect their function using single-molecule fluorescence approaches to directly observe chromatin dynamics as well as to monitor protein interaction dynamics in real-time. These methods allowed us to reveal fundamental mechanisms in gene repression, activation and DNA repair.
Controlling the chemical, mechanical and dynamic properties of microtubules is important for a host of key cell function, including cell division, transport, and cell polarity. PTMs of tubulin proteins (including poly-glutamylation and detyrosination) play a major role in this regulation. In analogy to our work on chromatin, in a collaborative NCCR project with the Aumeier and Gönczy laboratories, we developed a semi-synthesis method to produce tubulins carrying defined PTMs. These designer-tubulins, which represent unique novel tools in microtubule research, allow us now to dissect tubulin PTM signaling at unprecedented precision.