Department of Biology

Lab

Jordan Hall A315
(812) 856-2378
Lacefield Lab website

Awards

IU Trustees Teaching Award, 2013
Basil O'Connor Award, March of Dimes Foundation, 2010

Research

Errors in chromosome segregation can have devastating consequences. In mitosis, chromosomal instability is a hallmark of cancer. In meiosis, chromosome mis-segregation can result in trisomy conditions such as Down syndrome, the leading genetic cause of developmental disability. The goal of our research is to understand the mechanisms the cell uses to ensure faithful chromosome segregation in mitosis and meiosis. We are studying how the cell prevents errors in chromosome segregation, including how chromosomes properly attach to the spindle in both meiotic divisions and the monitoring of this attachment by the spindle checkpoint. Many of the genes involved in these processes are conserved, allowing us to use the powerful genetic tools of the budding yeast, S. cerevisiae.

Chromosomes attach to the meiotic spindle at the kinetochore, the protein complexes built on centromeric regions of DNA. We are interested in the proteins that regulate this connection in meiosis. For example, in the first meiotic division (meiosis I), the kinetochores on paired homologous chromosomes must be bound to microtubules from opposite poles of the spindle, but in meiosis II, the kinetochores of sister chromatids must be bound to opposite poles. Furthermore, to prevent chromosome missegregation, if the kinetochores on homologous chromosomes attach to microtubules from the same spindle pole, one kinetochore must release and re-attach properly. The spindle checkpoint monitors this connection and, if the attachment of microtubules to kinetochores is defective, halts the cell cycle to allow time to correct the error. We are studying the regulation of the proteins within the kinetochore to execute each of these steps: microtubule binding to homologous chromosomes in meiosis I and sister chromatids in meiosis II, sensing inappropriate microtubule attachment, signaling the checkpoint, and correcting the error.

In meiosis, the spindle checkpoint proteins not only act in a surveillance system to ensure that chromosomes are properly attached to the spindle, but they also have additional roles. Certain spindle checkpoint proteins are involved in ensuring that kinetochores can initially attach to the bipolar spindle. Other spindle checkpoint proteins are also involved in the timing of the meiotic cell cycle. We are interested in understanding how the different roles of the spindle checkpoint proteins are executed.