Studies by my laboratory focus on spindle and chromosome
dynamics, and the mechanisms that ensure proper chromosome
transmission and inheritance. We are especially interested
in molecular motor proteins and the roles of motors
in force production and dynamics of chromosomes and
spindles.
More than 10 years ago, my laboratory identified
a kinesin-related microtubule motor protein, Ncd,
that is required for normal chromosome distribution
in Drosophila. We showed using in vitro motility assays
that Ncd moves on microtubules towards the stable
minus ends, rather than towards the fast depolymerizing/polymerizing
plus ends, like conventional kinesin and other kinesin
motors. We recently determined the molecular basis
of the unexpected reversed directionality of Ncd movement
on microtubules and identified the region of the motor
required for minus-end movement. We also recently
identified a large conformational change of the coiled-coil
stalk of Ncd that we believe is involved in force
production and directed movement of the motor.
Our current efforts are to determine the mechanism
of Ncd function in chromosome segregation. We previously
localized the Ncd motor to meiotic and mitotic spindles,
and showed that ncd mutants exhibit highly abnormal
meiotic spindles and frequent loss of centrosomes
and chromosomes from mitotic spindles. These findings
imply that Ncd is needed for assembly of normal meiotic
spindles and attachment of centrosomes and chromosomes
to mitotic spindles. Using a fusion of Ncd to GFP,
we have followed spindle dynamics in live oocytes
and embryos - we visualized the meiotic divisions
in oocytes for the first time and followed mitotic
divisions in wild-type and mutant embryos. Microtubule
motors similar to Ncd probably exist in most or all
eukaryotes, where they perform roles in meiosis and
mitosis that include spindle pole formation, attachment
of centrosomes to spindle poles, and mediation of
poleward chromosome movement by sliding microtubules
and kinetochores poleward.
Students can participate in these studies by carrying
out molecular genetics studies to determine the mechanism
of Ncd function in the cell by constructing and analysing
specific mutants, or molecular and biochemical studies
to determine how the motor functions in vitro.
