Designable Modularity in Synthetic Biology: from New Protein Folds to Cellular Circuits

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Event details

Date 02.07.2018
Hour 12:15
Speaker Prof. Roman Jerala, National Institute of Chemistry, Ljubljana (SLO)
Location
Category Conferences - Seminars
DISTINGUISHED LECTURE IN BIOLOGICAL ENGINEERING
(sandwiches served)

Abstract:
Synthetic biology introduces engineering principles into biological or biomimetc systems. Construction of devices for a complex cellular environment requires orthogonal building elements with similar properties, which may be difficult to harvest from nature and combine into scalable functional devices. Designable modules can be constucted in many variants that can be used to build complex systems. I will present application of designable modularity for the construction of new protein folds and for the design of mammalian cell logic circuits. Orthogonal coiled-coil peptide dimers can be designed de novo and used for the construction of protein cages composed of a single polypeptide chain of concatenated coiled-coil building modules (coiled-coil protein origami - CCPO). CCPO represents a new type of protein folds not found in the nature, where the structure is defined by the order of interacting segments defining the final topology rather than by compact hydrophobic core as natural proteins. The second generation CCPOs demonstrated that diverse designed protein polyhedra can self-assemble bacterial or mammalian cells. The second type of designable modules are DNA binding domains that can be used to design transcriptional regulators, enabling construction of orthogonal genetic logic NOR gates. This allowed construction of all 16 two-input logic gates and toggle switches in mammalian cells. Additionally special properties of Transcription-activator like effectors for the polarized displacement were identified which can be used to construct new type of transcriptional regulation with advanced properties and for therapeutic applications.
 
Bio:
Dr. Roman Jerala is head of the Department of Synthetic Biology and Immunology at the National Institute of Chemistry in Ljubljana, Slovenia. He is also a full professor at the Faculty of Chemistry and Chemical technology, University of Ljubljana, synthetic biology project director at the Centre of Excellence EN-FIST and EMBO member. His research areas of interest include synthetic biology, designed bionanostructures and molecular mechanism of innate immunity. In 2013, his group published an article in Nature Chemical Biology on designed coiled-coil protein origami (CCPO) cages using reprogrammed bacteria by synthesizing a protein that folds itself into a tetrahedron measuring just 5 nanometres along each edge, which can be used as container for delivering drugs on the nanoscale. That paves a path to designing and producing completely new protein shapes. This work was recently extended by a second generation of CCPOs that are able to self-assemble in vivo, published in the Nature Biotechnology. Dr. Jerala received numerous awards including Pregl award by the National institute of chemistry for outstanding scientific achievements, Zois award for outstanding scientific achievements (the highest national scientific award) and Medal for services by the President of the Republic of Slovenia. He is internationally best known as the leader of Slovenian teams that won the Grand prize at the International Genetically Engineered Machine (iGEM) competition in 2010, 2008, and 2006 in addition to 5 Track winner awards.

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