Biophysical investigations of molecular recognition in high-throughput

In this project, we will study biomolecular binding and recognition in greater detail than ever before by developing state-of-the-art high-throughput methods to measure molecular binding and dynamical structure in vitro.

We will measure and quantify the affinity between 1000 paralogous transcription factor mutants and 100 DNA binding site mutants in a single experiment.

Using this data, we will construct sequence-dependent physical models and predictive deep learning models that explain how the sequence of the transcription factor and the DNA binding site are co-optimized for binding.The research will be conducted in my lab at Stockholm University and SciLifeLab Campus Solna.

I will serve as the project manager, and one PhD student will perform the research.

Year 1 of the project will be used to build the fluorescence microscope, to develop image analysis pipelines, and to design, purify, and fluorescently label transcription factor mutant libraries. In years 2-4 we will perform high-throughput binding measurements and build models from the binding data.

The research is important because it will provide a quantitative understanding of how genetic information codes for the binding of regulatory elements.

If we one day can accurately predict the binding patterns of transcription factors at arbitrary locations in the genome, it could revolutionize systems biology and provide a foundation for finding cures for many diseases, including cancer.