Research Questions
Our work is done by an interdisciplinary and collaborative team of curious biologists, mathematicians, engineers and biophysicists. We use multinucleate cells to understand how dynamic compartments can form in the cytoplasm and how cells know their own geometry. Although we are driven to discover the fundamental properties of cells, the work is relevant to the health of humans and the planet. We work in fungi and also human placenta because these systems share a specialized form of cell organization where many nuclei share a common cytoplasm.
What is the physiological role of biological phase transitions?
The spatial organization of cytosol is not well understood. Using the ability of nuclei to act independently despite sharing a common cytoplasm, we discovered that mRNAs and disordered proteins come together and condense to form droplets known as biomolecular condensates. These droplets position mRNAs near nuclei and sites of growth and we hypothesize regulate translation to create functionally distinct territories of cytosol. Current work in this area is focused on understanding how mRNA sequences encode the material properties of droplets, how cells control where droplets form, how the size of droplets is regulated and how cells use condensates to adapt to their environment. We are particularly interested in the role of RNA sequence and structure in the assembly of condensates and are testing the hypothesis that RNA sequence forms the basis of a physical code for cell organization.
How do cells sense their shape?
How do cells control the location, scale and shape of septin cytoskeletal assemblies on membranes?
Although it is well understood how cells change shape, little is known about how cells may sense their shape and use information about their geometry to localize signaling or make decisions. We have found that the septin cytoskeleton can assemble in a curvature dependent manner. Septins are highly conserved cytoskeletal elements that organize membranes, act as scaffolds and connect to other cytoskeletal networks. By polymerizing into filaments on the scale of microns, septins allow cells to perceive shape changes that are much larger than the size of individual proteins. We are trying to understand how septins sense different curvatures, how different cells may tune the curvature preference for septin assembly and how downstream signaling proteins are recruited to different types of septin assemblies. We are also focused on studying how cells determine the location, the shape and size of septin higher-order structures.
How do marine fungi survive extreme environments?
What new biology can be discovered in unstudied systems from extreme environments?
We have collected, identified and observed fungi from the waters in the vicinity of Woods Hole, MA to identify fungi that persist in the harsh conditions of the marine environment and present new problems in cell biology. Many of these fungi are extremophiles and have the potential to play critical roles in the ability of the biosphere to adapt to increasingly extreme and fluctuating environmental conditions. We are working to develop these fungi as model systems for cell biology to understand how they survive extreme conditions.
How does a tissue-sized cell in the placenta function?
The placenta is a temporary organ essential for human development. Exchange of nutrients and oxygen between mother and the fetus is achieved by a single, enormous cell with billions of nuclei called the syncytiotrophoblast. The multinucleated syncytiotrophoblast (STB) is a tissue-sized single cell. This giant cell facilitates the exchange of nutrients, is essential for fetal immunoprotection, is the primary producer of pregnancy hormones, and performs essential metabolic functions. What is the advantage of this specialized, multinucleate architecture? We hypothesize that the multinucleate organization of the giant STB enables individual nuclei to have specialized gene expression programs yet remain integrated by sharing a common cytoplasm. We are combining single nucleus sequencing and spatial transcriptomics along with organoid models to study the placenta. Our goal is to establish cell biology tools in the placenta so that we can understand the molecular basis of pregnancy-related disease.
