Sandra Gawlitt     email
Institution Helmholtz Institute for RNA-based Infection Research

Supervisor:
Prof. Dr. Chase L. Beisel (Würzburg)

Promotion Committee:
Prof. Dr. Chase L. Beisel (Würzburg)
Jun. Prof. Dr. Alexander Westermann (Würzburg)
Dr. Ana Rita Brochado (Würzburg)
Prof. Dr. Hardt (Zürich)

CRISPR-based combinatorial screens in bacteria
 

A ubiquitous but hard to explore phenomenon in biology is redundancy, where seemingly similar components drive a common process. With conventional methods, it can be very difficult to explore the functions of each of the individual components involved. However, CRISPR-based combinatorial screens enable us to target multiple genes at once. At this point, I will focus on two different projects.

First, I am interested to find redundant Hfq-associated sRNAs in Escherichia coli. Hfq serves as an essential chaperone for small RNAs (sRNAs) in E.coli. About 100 sRNAs have been identified that modulate RNA stability and translation through short imperfect base-pairing interactions. Each of those sRNAs can have 10-100 targets and they are involved in regulatory responses to environmental stress. However, deletions of single sRNAs in E.coli show only minor effects compared to an hfq deletion mutant, which shows pleiotropic growth defects. It would be interesting to reveal defined sets of sRNAs that can recapitulate the growth defects of E. coli lacking Hfq.

The second collaborative project will deal with Salmonella Typhimurium pathogenicity island two (SPI-2) type III secretion system (T3SS) effectors. The translocation of effector proteins via the SPI-2 T3SS enables bacterial replication within the host cells. I am interested to discover the function of defined sets of effector genes during intracellular replication. Therefore, I will create a number of proposed functional mutants and eventually, we will evaluate their replication ability in mice models.