shape of an animal cell is determined through a dynamic interplay between
intrinsic information and cues from the extracellular environment. In the Baum
lab we are exploring the molecular, cellular and physical processes that shape
isolated animal cells, cells in developing tissues, and dividing human cancer
cells. To do so, we study cells in fruit flies, cells in culture as well as cells
isolated from cancer patients using an array of interdisciplinary approaches
including molecular biology, genetics, high-content RNA interference (RNAi)
screening, live cell imaging, automated image analysis, microfabrication,
biophysical techniques and computational modeling. In this way we aim to better
understand how dynamic changes in the form of individual cells shape tissues during
normal development and homeostasis, and contribute to metastatic cancer.
Cancer is a disease in which
individual clones of mutant cells expand without control even when spread far
from their tissue of origin. This is made possible by mutations acquired by
cancer cells during tumour evolution that break their normal dependency on the
local cues which usually function to ensure that the behaviour of each cell is
finely tuned to the requirements of its host tissue. As a result, while normal
cells only divide to maintain tissue homeostasis, during tumour evolution
cancer cells acquire a novel ability to divide under a range of conditions: in
the face of compressive forces in a growing tumour and, to establish
metastases, in new, poorly structured environments.
By carrying out a detailed study
of mitotic rounding and cell division in different contexts, a major goal of
our research is to better understand the molecular and cellular mechanisms that
make cancer cells both blind and resilient in the face of a changing
environment. Mechanics plays a key role in this process, since the act of cell
division is involves a series of dramatic actomyosin-dependent changes in cell
shape and size. These begin at the very start of mitosis as cells stop moving,
de-adhere from the substrate and round up to form rigid swollen spheres that
provide a safe space in which to construct and orient their bipolar spindles.
Then, once anaphase is triggered, cells elongate through polar relaxation as
chromosomes move apart, before dividing into two as they exit mitosis.
Ultimately, by characterizing the
genes and the biochemical, physical and geometrical constraints affecting the
mitotic progression in both normal and cancer cells we hope to identify novel
diagnostic and prognostic markers of cancer progression, and to identify
strategies by which to selectively kill dividing metastatic cancer cells.
identical twins tend to look remarkably similar. How the genome guides cell
behavior during development to ensure this remains poorly understood. To get at
this process we are trying to understand how actin-dependent changes in the
shape of individual epithelial cells give rise to a well-ordered tissue during
the completion of the development of the dorsal thorax of the fruit fly - a
process we like to call tissue refinement. In recent work, using a combination
of live cell imaging, genetics and computational modeling, we have used this approach
to demonstrate a role for basal filopodia in tissue patterning and for
epithelial cell delamination in the refinement of cell packing.
We are currently recruiting a post-doc to study the mechanics of cell division. If you are interested, please contact us.