Download Understanding selectivity in the CRISPR CAS9 system

UROP Project Title: Understanding selectivity in the CRISPR-CAS9 system
Supervisor: Dr. Stefano Angioletti-Uberti, Materials
Description: Gene editing using the CRISPR-CAS9 technology relies on selective recognition of specific
nucleotide sequences using a matching RNA of 21 base-pairs. In this system, off-target binding must
be reduced to a minimum because its occurrence can lead to modifications of genes rather than the
one effectively targeted, with unpredictable consequences. Hence, an important question is to
understand what are the intrinsic limits in terms of targeting selectivity that such system must have.
For example, can we expect the same degree of off-target binding for all possible sequences? Can we
improve targeting selectivity using a longer / shorter recognition sequence (...or why did Nature
choose exactly 21 bases?). In this project, we will build a simple statistical mechanical model trying to
incorporate the main feature of DNA-RNA binding, and use it to explore these and other questions,
comparing results to experimental data whenever available.
The interested student should have a strong foundations in mathematics, and the will to learn the
basis of statistical mechanics. Ability to code in any object-oriented language, e.g. Python, and some
knowledge of the Unix/Linux operating system will be beneficial for the completion of the project, but
a driven student can also acquire these skills during its execution.