Centre Seminar Series

Invited external speakers

27 February 2025

Erin Cutts (School of BioSciences, University of Sheffield)

Title: Regulation of the Key Chromosome Components: Condensin, Cohesin and TOP2a

Abstract: During mitosis, cells must faithfully segregate meters of entangled DNA into two daughter cells. To do this, DNA is untangled, packaged into chromosomes, and the copied chromosomes are held together at the centromere until the cell is ready to divide. Errors in this process cause genome instability and are associated with human disease, such as developmental disorders and cancer. Three protein complexes; condensin, cohesin and Topoisomerase 2a are essential to this process. Condensin spools DNA into loops to form chromosomes, Topoisomerase 2a untangles the DNA, and cohesin holds the copied chromosomes together. My work has investigated the regulation and mechanism of these crucial proteins. By employing a combination of biochemistry and single molecule approaches I have examined how condensin complexes are activated at the start of mitosis and visualised how cohesin prevents Topoisomerase 2a from untangling DNA.

Host: Davide Michieletto

Cutts Lab

FRIDAY 14 March 2025

Christophe Danelon (TU Delft)

Title: Building a Synthetic Cell via Evolution

Abstract: Our group is engaged in the long-term effort to build an entire living cell using a bottom-up synthetic biology approach. We envision the chassis of a synthetic cell as a reconstituted gene expression system, called PURE system, encapsulated inside a lipid vesicle compartment. Our latest results on synthetic genome assembly, DNA replication, phospholipid biosynthesis, and liposome constriction will be presented. Moreover, we will see how directed evolution can accelerate the optimization and functional integration of these biological modules. The challenges to create an autonomously replicating synthetic cell and the great opportunities that may arise by using automated experimentation and active learning, will finally be discussed.

Bio: I was trained in chemistry and physics at the University of Toulouse, France. After a PhD in biophysics at the Institute of Pharmacology and Structural Biology in Toulouse (2003) and a post-doctoral stay at the EPFL Lausanne, Switzerland, I started my lab at the TU Delft, Netherlands, in 2010. My group pioneered experiments in the reconstitution of DNA-programmed cellular functions, such as DNA replication, membrane synthesis, and liposome constriction. In 2023, I relocated my lab at the Toulouse Biotechnology Institute, France. Our Synthetic Cell Lab (danelonlab.com) is engineering synthetic genomes and is developing new technologies for continuous evolution of synthetic cells using AI (active learning) and lab automation.

Host: Nadanai Laohakunakorn

Danelon Lab

27 March 2025

Barbara Di Ventura (Institute of Biology II (Faculty of Biology), University of Freiburg)

Title: A question of dynamics

Abstract: In response to different stimuli many transcription factors (TFs) display different activation dynamics that trigger the expression of specific sets of target genes, suggesting that promoters have a way to decode dynamics. In this talk, I will present results based on a light-responsive synthetic TF, which we built using well-characterized components and LINuS, a blue light-dependent nuclear localization signal previously developed in our lab. I will show how we used this system to directly manipulate the nuclear localization of the synthetic TF in mammalian cells, generating two different pulsatile and sustained TF dynamics. Using live cell microscopy and mathematical modelling, we analysed the behaviour of a library of reporter constructs and found that decoding of TF dynamics occurs only when the coupling between TF binding and transcription pre-initiation complex formation is inefficient. We also found that the ability of a promoter to decode TF dynamics gets amplified by inefficient translation initiation. Using the knowledge acquired, we built a synthetic circuit that allows obtaining two gene expression programs depending solely on TF dynamics. Finally, I will show how our findings with the synthetic TF can be applied to two natural TFs: p65 and p53. These results help elucidate how gene expression is regulated in mammalian cells and open up the possibility to build complex synthetic circuits steered by TF dynamics.

Host: Filippo Menolascina

Di Ventura Lab

17 April 2025

Mark Howarth (Department of Pharmacology, University of Cambridge)

Title: Protein Superglues to control cells and protect from outbreak threats

Abstract: Many properties of antibodies and other binding proteins are limited by dissociation. A special feature of the bacterium Streptococcus pyogenes enables spontaneous locking together of its surface proteins. Our lab re-engineered this system to generate an irreversible peptide-protein interaction (SpyTag/SpyCatcher). This superglue is genetically-encodable and specific in diverse biological environments. We accelerated reactivity to the diffusion limit and generated variants switchable by light, pH or temperature. SpyTag allows rapid reformatting of antibodies with reporters or effector molecules. SpyTag and its related superglue SnoopTag allow programmable synthesis of antibody/nanobody teams for multiplex control of cell signaling. SpyTag also enables simple reformatting of CAR-T cells, virus-like particles for vaccination, or viral vectors. We have developed an independent bacterial superglue called NeissLock for covalent reaction to unmodified human proteins via an anhydride. Applications will be discussed towards cell therapy and for broad protection against long-standing vaccine challenges and emerging pandemic threats.

Host: Lynne Regan

Howarth Lab