Our lab is interested in how cells solve geometry problems.
Cells are not bags of enzymes, they have complex three dimensional structures. But where does the information come from that determines the structure of a cell? Why do different cell types have different architectures, and how does the structure of a cell affect its function? These are fundamental questions whose answers remain largely unknown. Our goal is to ask how cells solve specific types of geometry problems, focusing on the organelle as a fundamental unit of cellular organization. What determines the size, shape, number, and position of organelles? Answering these questions is what drives our science.
Lab Philosophy - focus on questions
Because our lab is driven by conceptual questions and not by interest in any one specific organelle or model organism, we tend to take a variety of approaches, always seeking the simplest possible system in which to study a particular type of geometry problem. For example, in our study of organelle size, we began by studying length control of cilia and flagella, because these organelles are essentially one-dimensional, making size control particularly easy to study. As we extend our study to size control of other organelles, we turn to mitochondria and vacuoles which have technical advantages in terms of the simplicity of their shapes. We also do not hesitate to switch between model organisms as the need dictates. For studying cilia and flagella, we mostly use Chlamydomonas reinhardtii, a green algae with genetics similar to yeast. We choose this organism because it is the easiest organism to work with that actually has cilia and flagella (yeast, regrettably, do not). But for organisms that are found in yeast, we use yeast itself in order to exploit the full power of yeast genetics. For other questions we employ other organisms, such as Stentor coeruleus to study how cells regenerate.
Current Projects in the Lab
How Cells Control Organelle Size
- regulation of flagella length in chlamydomonas
- vacuole size scaling in budding yeast
- ciliary disease genes and length control
- pathways altering organelle size in cancer cells
Pattern Formation and Regeneration in a Single Cell
- Stentor genome
- development of RNAi methods for Stentor
- how do cells restore proportionality during regeneration?
- how do cells know when a piece has been removed?
- how do cells establish long range body axes in a 1 mm long cell?
How Cells Count
- mechanism of centriole duplication
- regulation of centriole copy number
- assembly of the centriole proteome into macromolecular structures
- centriole function in cell division and organization
How Cells Tell Direction
- centriole orientation
- left/right symmetry breaking by ciliary movement
- how centrioles find position within cells
- mirror symmetry between sister cells
- modeling role of spindle orientation in tissue development