Research group: Structural Characterization of Macromolecular Assemblies
My career revolves around my interest in the structures of nucleic acids –including design, selection, and modifications, to understand the roles in living organisms and how we can influence their functions.
It started with my Bachelor studies at the University of Wroclaw, where one of my voluntary practices lead to my work on aptamers – DNA/RNA molecules, able to specifically recognize defined sites and bind them (analogically to the amino acid-based antibodies). For my Master’s degree, I moved to the University of Glasgow and worked on serine recombinases (enzymes able to cut, rotate and ligate two dsDNA strands). After this, I went to Poland and for almost two years and worked in the International Institute of Molecular and Cell Biology in Warsaw, learning RNA crystallography in the context of bacterial riboswitches (a relatively primitive gene expression regulation system, in which RNA, upon binding a small molecule, changes its conformation regulating gene expression). Since 2019, I am carrying out my PhD studies thanks to a BIST COFUND Marie Skłodowska-Curie PhD fellowship, in the Institute for Research in Biomedicine in Barcelona. Here, I work in the Structural Characterization of Macromolecular Assemblies (Macias Lab) on the characterization of Smad interactions with cofactor proteins, DNA and RNA, using biochemical and biophysical assays and structural biology.
In the course of my career I’ve also undertaken many voluntary activities in various areas, such as teaching (high school meetings, Crazy in Biomedicine 2020), public health (COVID-19 testing program Orfeu by the Generalitat de Catalunya) or art (IRB Barcelona’s Artist in Residence).
In our laboratory, we are focused on deciphering the mechanisms that correlate cell signaling with gene expression. We also aim to discover how these mechanisms are regulated and how to tackle the problems created by their misregulation – which, unfortunately, often leads to the development of patient’s oncological condition.
The transforming growth factor β (TGF-β) family of cytokines regulates critical processes during the lifecycle of metazoans. Gene responses activated by TGF-β cytokines play important roles in embryo development, tissue homeostasis, repair, and immunity. The main TGF-β cellular signal transduction mechanism is the Smad protein pathway, and mutations in the components of this pathway are responsible for various inherited and somatic diseases. Formation of large nuclear assemblies of Smads with chromatin remodelers and master transcription factors directs these molecular machines to binding-sites of gene promoters and enhancer regions, tuning their function to the cellular context.
As a structural biologist, through mainly crystallography, I look at biomolecular interactions at an atomic scale. From this point of view, I try to understand and describe the roles of these protein complexes in human health and disease. I also plan to complement this in vitro knowledge with additional information obtained from experiments performed in cancer cell lines.
As the aim of my PhD, I want to expand our knowledge about the structural characterization of Smad protein interactions with selected cofactor proteins and nucleic acids. Supported by this knowledge, I plan to identify small molecules that can influence the formation of Smad complexes; possibly identifying binding hotspots. Inhibition or reinforcement of these complexes can have potential applications in both chemical biology and/or medicinal chemistry studies.