Research

The main focus of our lab is on clathrin structures. We want to understand the molecular mechanisms behind the interplay of these structures with the actin cytoskeleton during endocytosis and with integrin αvβ5 during the establishment of reticular adhesions.

The Endocytic Cytoskeleton

There are a lot of unanswered questions on how the cytoskeleton surrounding endocytic structures are formed, organised and regulated. Many of these questions are described in our recent review (Abouelezz & Almeida-Souza, EJCB 2022), where we propose the term “endocytic cytoskeleton”. Beyond its importance in the endocytic process, the endocytic cytoskeleton is an interesting system to understand actin biology in general, as it is process where the formation of actin networks has a well-defined start and end point. We currently have projects in the lab trying to tackle some of these questions. 

 

Reticular Adhesions

We have recently discovered that flat clathrin lattices are required for the formation of reticular adhesions (Hakanpää, JCB 2023). We also found that the extracellular matrix protein fibronectin inhibits reticular adhesions via activation of its receptor (integrin α5β1) and that the onset of cell migration is accompanied by the disappearance of these structures. Reticular adhesions were only recently discovered (Lock, NCB 2018) and they differ from typical focal adhesions for their higher stability, lack of direct connection to the actin cytoskeleton and absence of classical markers (paxillin/talins/FAK and etc). Results from our lab and from others suggests that reticular adhesions are markers of non-migrating cells. One could say that reticular adhesions are counter-migratory structures. We have a series of projects in the lab trying to understand the details of how these structures are formed, regulated and their role in cell migration during development and cancer.

 

Others

It would be disingenuous to say that we don’t dabble on other projects. We are curious and creative people and we like to try new things, develop new methods and sometimes we follow our noses into directions that are not the core of our science. 

 

Our Phylosophy: Be kind

In my lab, we work as a family. I enforce respect, cooperation and kindness towards lab members and everyone around us (Almeida-Souza & O’Brien, TCB 2022). I actively participate in the projects by doing experiments, data analysis and regular discussions on results. I encourage cross-project collaborations, a relaxed atmosphere, and a healthy work-life balance. I know that relaxed and engaged people produce better science. 

 

Typical techniques we use (or have used) in the lab

CRISPR/Cas9, microscopy (confocal, live cell imaging, super-resolution microscopy), cell migration assays, protein biochemistry, FACS, in vitro reconstitutions, Crystallography, CryoEM.