What do we study in our lab


In our lab we study Morphogenesis and Cell Junctions. Broadly speaking our work combines three important fields of biology: Cell Biology, Developmental Biology, and Genetics. Our lab does basic research, we want to find out the fundamental mechanisms that operate in nature. Nonetheless our work does have clear medical relevance because understanding the basic processes the regulate life is essential to developing better treatments for diseases. In our lab we are committed to using a Multidisciplinary approach. We are systems biologists and employ a wide array of techniques from genetics, genomics, cell biology, high resolution and quantitative imaging, biochemistry, molecular biology, biophysics, mathematical and theoretical biology, and many other fields.  


the main question our lab seeks to answer is this:


How are tissues and organs built over the course of development and how their complex structure is maintained throughout the life of an organism.


Our lab studies three main things: A family of proteins called Integrins that help cells stick in place, the role of cell junctions in stem cell biology, how muscles function is maintained throughout the life of an organism.


Why is studying integrins important?


From a reductive point of view, human-beings are nothing but trillions of cells. And yet, we have complex structures and shapes. So, why don’t we look like an amorphous blob of cells? How do we form these three-dimensional shapes?


Achieving such a complex body organization requires cells to be able to make both transient (short-term) and stable (long-term) adhesive contacts with each other (cell-cell adhesion) and with their extracellular environment (cell-extracellular matrix, or ECM, adhesion).


In animals and humans, cells attach to their environment through the action of cell junctions. These are big complicated structure containins many different types of proteins that fall into three basic categories: (i) adhesion receptors that span the plasma membrane and interact with both the extracellular and the intracellular environments; (ii) cytoplasmic linker proteins that directly bind to the adhesion receptor and act as an adapter to other intracellular components; and, (iii) cytoskeletal linker proteins that connect the adhesion complex to the cytoskeleton. The most common family of adhesion receptors that mediate Cell-ECM adhesion in animals are integrins.


Integrin-mediated attachment of the cell to the ECM is essential for a wide variety of biologically important events and is implicated in pathological disorders such as skin blistering diseases, muscle degeneration, thrombosis, blood clotting disorders, and cancer.


Why do we use flies?

The fly serves as a powerful model system for studying integrin function. Components of integrin-mediated adhesion are structurally and functionally very similar to their vertebrate counterparts so what we learn from flies gives us important clues about what integrins do in humans.


Compared to vertebrate genomes the fly genome is simpler. Thus, there is less redundancy for specific molecules. Furthermore, there are fewer components of the integrin adhesion complex. Both these factors make disrupting integrin-mediated adhesion much more easy. The fly is a genetically tractable model system that allows in vivo studies of integrin function during development on the level of the whole organism. Moreover, there is a wide array of available reagents including mutants, antibodies, and transgenic constructs to facilitate the study of integrin function in flies.


We believe that what we learn about integrins in the fly will not only provide us with basic insight into how animals develop and retain their structure throughout their life but also allow us to gain knowledge that will help improve human health.


What are we trying to find out about integrins?


We have three general goals: (i) we want to understand how the how integrins mediate cell adhesion, (ii) we want to understand how integrin adhesion is regulated and (iii) we want to understand how integrin-mediated adhesion is used during the life of an organism to establish and maintain complex 3 dimensional cell shape.

Research

How is muscle function maintained throughout the life of organism


Fly muscles provide an excellent in vivo model system to explore integrin-mediated adhesion in the context of the whole organism. We study how muscles are attached to the tendon cells. The structures that maintain muscle-tendon attachment are very well conserved between flies and humans. Mutations in the human that affect some types of integrin cause a muscular dystrophy. What we learn from studying fly muscles will teach us a lot about how human muscles function. The picture below shows fly muscles stained in red with the sites where muscles attach to tendons in green. The fly vascular system is stained in blue.

What is the role of cell junctions in regulating stem cel function


Stem cells are essential in animal development for the maintenance and regeneration of tissues. Our lab studies germline stem cells (the stem cells that make sperm and eggs) and somatic stem cells (the stem cells that make the cells whose job is to help sperm and egg be made). We use the fly testes which is excellent and well established model to gain fundamental insight into how stem cells are regulated. Its well established that in the fly the testes, germline stem cells (GSCs) are regulated through interactions with their surrounding somatic cells. We want to understand the mechanisms that role of different kinds of cell junctions in helping these two populations of cells to talk to and regulate one another. We aim to understand the function of cell junctions in the testes using genetics to explore links between cell junctions and the cell signaling pathways that regulate stem cells in the fly testes.