Structure of Macromolecular Assemblies

Our group aims to unveil the structure of cellular machines to gain mechanistic insight into macromolecular function and assist the development of biomedical applications. For this, we use electron cryomicroscopy (cryo-EM) and X-ray crystallography, both providing information to atomic resolution, combined with other biophysical and biochemical techniques. This integrative methodology is applied to study essential cell processes such as genome transcription, DNA repair, DNA integration and cell division.

Genome transcription

The transfer of genetic information encoded in DNA is the main determinant of gene expression. Alterations in this process have significant impact on cell homeostasis and are directly related to disease. RNA polymerases transcribe the genetic information from DNA to RNA, by catalyzing the addition of nucleotides that are complementary to the DNA template strand. Eukaryotes require three different RNA polymerases, each transcribing a specific set of genes. We focus on the study of RNA polymerase I and various transcription factors that regulate gene expression. Further details can be found [here].

DNA damage detection and repair

DNA damage threatens cell life and must be repaired to maintain genome integrity. Transcription is particularly sensitive to DNA damage and, hence, it is linked to DNA repair. Different lesions induce RNA polymerase stalling, which activates the recruitment of DNA repair factors, including endonucleases XPF and XPG to eliminate the lesion. Alterations in these repair factors associate with genetic disorders such as xeroderma pigmentosum and Cockayne syndrome. We focus on the study of lesion detection by RNA polymerases and damaged DNA elimination by XPG. Further details can be found [here].

Directed DNA integration

Transposable elements are DNA sequences that can change their position within genomes. Their movement drives the development of new cellular functions, but it can also produce harmful mutations. To minimize deleterious effects, retrotransposons insert into safe regions of the genome through tethering of their integrase to proteins operating on the chromatin, such as RNA polymerases. Further details can be found [here].

Bacterial cell division

Cell division is an essential biological process that enables propagation of living organisms. Bacterial division involves protein assembly into the divisome, which coordinates membrane invagination and synthesis of the cell wall, finally giving rise to two daughter cells. As such, bacterial cell division proteins are targets for the discovery of new antibiotics, which are needed to fight resistant bacterial pathogens. We focus on the study of FtsZ, an ancestral tubulin homologue playing a central role in bacterial cell division. Further details can be found [here].