Stefano Stella

Short presentation

My research is focused on the identification and functional characterization of molecules such as CRISPR-Cas complexes, TALE/BuDs and homoendonucleases that can be used in precise genome manipulation applications.

To understand the molecular details that regulate the interaction between nucleic-acids and the proteins, I employ molecular, structural, and cell biology techniques. At present, my projects are:

• CRISPR-Cas12a (Cpf1) is able to recognize and cut specific DNA target with high specificity. We use biochemistry, X-ray crystallography, single molecule cryoEM and single molecule FRET to understand the mechanism of action of Cas12a.
• Variants of Cas12a protein are present in several types of bacteria. Cleavage analysis of these variants indicate that these proteins cut the DNA target in different positions. We use NGS and structural approaches to understand the molecular details of these differences and how to harness these features into genome manipulation tools.
• CRISPR systems are divided into two classes; class 1 that uses multi-subunit complexes to recognize and cleave the target nucleic-acids, and class 2 that achieves the same function by using a single protein. We use HPLC analysis, X-ray crystallography and cryoEM to study the mechanism of action of these multi-subunit complexes.
• CRISPR-Cas system can be found in many archaea and bacteria. We use genomic metadata analysis and RNAseq to identify and characterize new types of CRISPR-Cas class2 systems.

Selected publications

A Type III-B Cmr effector complex catalyzes the synthesis of cyclic oligoadenylate second messengers by cooperative substrate binding. Han, Wenyuan; Stella, Stefano; Zhang, Yan; Guo, Tong; Sulek, Karolina; Peng-Lundgren, Li; Montoya, Guillermo; She, Qunxin. Nucleic acids research, 20.09.2018.

Class 2 CRISPR-Cas RNA-guided endonucleases: Swiss Army knives of genome editing. Stella, Stefano^*#; Alcón, Pablo^*; Montoya, Guillermo^#. Nature Structral and Molecular Biology Vol. 24, No. 11, 11.2017, p. 882-892.

Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage. Stella, Stefano^*#; Alcón, Pablo^*; Montoya, Guillermo^#. Nature, Vol. 546, No. 7659, 22.06.2017, p. 559-563.

Visualizing phosphodiester-bond hydrolysis by an endonuclease. Molina, Rafael^*; Stella, Stefano^*; Redondo, Pilar; Gomez, Hansel; Marcaida, María José; Orozco, Modesto; Prieto, Jesús; Montoya, Guillermo. Nature Structural and Molecular Biology, Vol. 22, No. 1, 01.2015, p. 65-72.

CV

Current position

2014-               Associate Professor at the Novo Nordisk Foundation Center for Protein Research (CPR). University of Copenhagen, Copenhagen (DK)    

Previous positions

2011-2014       Staff scientist at the Centro Nacional de Investigaciones Oncológicas (CNIO). Madrid (ES)

2010-2011       Post-Doc at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC). Strasburg (FR)

2005-2010       Post-Doc at the Department of Biological Chemistry; University of California Los Angeles (UCLA). Los Angeles, (USA)

2001-2005       PhD student at the Dep. Genetics and Molecular Biology; University of Camerino (UNICAM) Camerino (IT) and at the Max-Planck-Institut für molekulare Genetik, Berlin (DE)