Fysikaliska principer för genetiska regulatoriska koder

Tidsperiod: 2017-01-01 till 2022-12-31

Projektledare: Johan Elf

Medarbetare: Sebastian Deindl, Maria Tenje, Magnus Johansson, Lynn Kamerlin, Shina Ca Kamerlin, Shina Caroline Lynn Kamerlin

Finansiär: Vetenskapsrådet

Bidragstyp: Stöd till forskningsmiljö

Budget: 23 382 000 SEK

The mechanisms for decoding the genome’s regulatory sequences are far less understood than the mechanisms for encoding the structure and function of the regulated macromolecules. The focus of the environment is therefore to identify the principles and physical limitations for specificity and speed in accessing selected genetic information in the vast background of chemically similar sequences. This challenging question will be addressed by an interdisciplinary team of young scientists, combining kinetic measurements in living cells, in vitro single-molecule microscopy, and molecular dynamics simulations. In particular, we need to develop two new enabling technologies. The first is an opto-fluidic approach for connecting genotypes to complex phenotypes at library scale using high-resolution microscopy and in situ sequencing; the second is a technology for studying ultra-fast kinetics in living cells using single molecule tracking with polarization readout. In order to implement these new technologies, we need to work closely with skilled staff engineers throughout the duration of the project. For this reason, the endeavor is not possible without long term funding of the environment. The future applications of this research will be increased specificity in genetic therapy and optimized production of complex biomolecules. However, already at the end of the funding cycle the new technologies will transform our way of approaching the molecular basis of living matter.