Andreja MajerleView all speakers
Andreja Mjerle is a member of the Laboratory of Biotechnology at the National Institute of Chemistry in Ljubljana (Slovenia). She has long-standing expertise in synthetic biology as a member of Slovenian teams that have successfully competed in iGEM in 2006-2012. Her doctoral thesis in 2001 was in the field of innate immunity. She is a coauthor of an international patent on antimicrobial peptides.
Her current research interests focus on genetic logic gates and switches in mammalian cells and the development of a system for treatment of viral infections. In addition to research, she has a strong record of working with undergraduate and graduate students of the University of Ljubljana.
Electronic computer circuits consist of a large number of connected logical gates of the same type, such as NOR or NAND, which can be easily fabricated and which can implement any logical function. In contrast, transcription factors as the biological mediators of the cellular logic act on the whole set of binding sites within each cell. The complexity of designable genetic regulatory circuits is therefore limited by the availability of orthogonal transcription factors. The diversity of modular TAL (transcription activator-like) DNA binding domains is almost limitless. Here, we introduce designed orthogonal NOR gates based on TAL repressors as the universal scalable logical functions. Binding site for the designed TAL repressors were positioned upstream of the promoter, which decoupled the effect of any particular sequence on the transcription level variability. We implemented all 16 two-input logical functions within mammalian cell from combinations of TAL repressor-based NOR gates. According to Alan Turing the universal computing machine must be able to accept as input data values as well as instructions that define which logical functions should be performed on those data values. We constructed a genetic logical circuit composed of NOR gates, where one input is used to select execution of either AND or OR function over the two data inputs, demonstrating the principle of an universal biological computation device in mammalian cells. Biological genetic networks employing orthogonal designed NOR gate can therefore be used to implement in principle any logical function within mammalian cells to engineer a complex cellular response.