Determining Biofilm Structure by Deep Mutagenesis

Group: Protein phase transitions in health and disease and Bacterial infections: antimicrobial therapies.
Group leader: Benedetta Bolognesi (bbolognesi@ibecbarcelona.eu) and Eduard Torrents (etorrents@ibecbarcelona.eu)

Research project


Amyloid fibrils are best known for their implication in protein misfolding diseases. However, it is now clear that, for some proteins, these fibrillar structures can be conserved and functional. Examples of functional amyloid or amyloid-like fibrils are widespread in bacteria and fungi, where they often build the key structural support of the extra-cellular matrix of biofilms. Bacterial and fungal biofilms can enhance the pathogenicity of these microorganisms by increasing survival, invasion, cell adherence and resistance to antibiotics. The presence of biofilms was also shown to facilitate interactions among different type of micro-organisms. In this project we will use deep mutational scanning to quantify the effect of thousands of single and double mutations in a set of proteins forming biofilms. On the basis of the pattern of interactions among mutations, we will predict the structure of bacterial and yeast biofilms, their interactions and we will then validate these structures with a set of targeted downstream experiments. Overall, by uncovering the yet-uncharacterised key structural contacts in biofilm matrices, the results of this project will provide the basis to design therapeutics strategies aiming at highly destabilising or impairing biofilm formation.

References:

Bolognesi, B. et al. The mutational landscape of a prion-like domain. Nat. Commun., 2019.
Blanco-Cabra, N. et al. Novel Oleanolic and Maslinic Acid Derivatives as a Promising Treatment against Bacterial Biofilm in Nosocomial Infections: An in Vitro and in Vivo Study. ACS Infect. Dis., 2019.

Job position


The student will carry out this project across two labs at Institute for Bioengineering of Catalunya, member of the Barcelona Institute of Science and Technology (BIST). The deep mutagenesis design and data analysis will be carried out in the “Phase Transition in Health and Disease” Group (PI: Benedetta Bolognesi), while the optimization of the microbiological selection experiments will be performed in the “Bacterial Infections: Antimicrobial therapy” Group (PI: Eduard Torrents). The student will therefore have access to the best training in all aspects of the project, ranging from genomics to yeast/bacterial genetics and biofilm characterization.

The project will develop thanks to the IBEC research facilities and rely also on the CRG/CNAG sequencing unit. Previous experience in microbiology, biophysics and genetic engineering will be positively evaluated. A strong interest in developing both experimental and computational skills is required. The student will have access to a PhD program that includes transferable skills training in addition to scientific and technical courses and will actively participate to IBEC seminars and Symposia.

Across the two labs, the ranges of systems and approaches employed vary greatly, hence providing the student with multiple options to identify the best system and approach at each stage of the project and the possibility to acquire additional types of expertise.