For information on PhD studies at TLL, click HERE
Research Interests
- Cell
Cycle Control
- Cytokinesis
- Mitosis
- Morphogenesis
- Cell Physiology
- Yeast Genetics
Research Projects
My group is interested in understanding the mechanisms regulating the physical division of one cell into two. This process, referred to as cytokinesis, requires the function of an actomyosin based contractile ring in several organisms. We use the fission yeast Schizosaccharomyces pombe as
a model to understand this process.
In fission yeast,
the actomyosin ring is assembled at the medial
cortex upon entry into mitosis and constricts upon
mitotic exit. We are interested in understanding
several questions relating to this process.
1. How is the actomyosin ring assembled starting
from its constituents? 2. How is actomyosin ring
constriction regulated? 3. How are the new membranes
and cell wall assembled in coordination with actomyosin
ring constriction? And 4. What are the cellular
responses to a failure in cytokinesis? We are using
a combination of several methodologies, including
genetics, cell biology, functional genomic and
biochemical approaches to answer these questions.
In
the recent years, we have characterized a type
II myosin important for cytokinesis. We have
shown that the actomyosin ring is assembled from
a myosin II containing progenitor spot. This
spot is present throughout interphase and its
components are incorporated into the actomyosin
ring. Furthermore, we have shown by FRAP analysis
that the myosin II progenitor undergoes minimal
turnover and exchange of components, unlike the
actomyosin ring, which undergoes dramatic turnover.
To further understand this progenitor spot and
its role in actomyosin ring assembly, we have
purified myosin II associated proteins and identified
several components by MALDI-TOF as well as ICAT
approaches in collaboration with Rudi Abersold’s
group (U Washington). We are currently further
characterizing the components in order to understand
the mechanism of actomyosin ring assembly.
We and others have recently made the discovery that components of the actomyosin ring turnover dramatically throughout the process of cytokinesis. We are attempting to understand if this observed turnover has a functional role.
We have made the discovery that lipid-raft like domains exist at the site of cytokinesis in fission yeast. We have also identified a novel protein Pal1p important for polarized growth during interphase and cytokinesis as well as Cps1p, a protein important for division septum assembly. We have also identified Cdc15p, a protein essential for cytokinesis, as a membrane component. We are trying to understand the role of lipid-rafts and other membrane domains in regulating cytokinesis via Cps1p, Cdc15p, and other proteins.
We
have identified a second pathway for actomyosin
ring assembly, which ensures cytokinesis is completed,
upon mild damage to the cytokinetic apparatus.
This actomyosin ring reassembly mechanism requires
the function of a protein phosphatase Clp1p and
the SIN, a conserved signaling network important
for cytokinesis. This “cytokinesis checkpoint” ensures
that the actomyosin ring is maintained for a
prolonged period of time and also prevents mitotic
entry of the two nuclei that are present in the
same cytoplasm. In a functional genomics based
approach, we have deleted all genes encoding
protein kinases and have identified a protein
kinase, Lsk1p, that is important for the maintenance
of the actomyosin ring, in response to weak cytokinetic
defects.
We believe these divergent studies will converge to generate a thorough appreciation of the spatial and temporal regulation of cytokinesis. These studies may also be applicable to related processes in other organisms.
|
