Ciencia Puerto Rico

The primary purpose of mitosis is the accurate segregation of genetic material. This is accomplished by a macromolecular machine, the mitotic spindle, which uses dynamic microtubules (MTs) and mitotic motors to separate chromosomes by orchestrating chromosome-to-pole motility (anaphase A) and spindle elongation (anaphase B).  Our lab studies mitosis in Drosophila syncytial embryos to learn how the anaphase spindle functions as a macromolecular machine to elongate itself and pull apart sister chromosomes, and thus to provide insights into how defects in its function can give rise to genomic instability, birth defects and cancer.

Data from our laboratory [1-7] suggest that before anaphase B onset the spindle achieve its steady-state length by balancing two opposing forces acting in concert: (1) an interpolar MTs (ipMTs) sliding mechanism pushing the spindle poles apart, generated by the homotetrameric kinesin-5 motor KLP61F, and (2) depolymerization of ipMTs at the spindle poles, generating poleward ipMT flux. Our working model suggests that, in response to cyclin B degradation at the end of anaphase A: (i) a MT catastrophe gradient causes ipMT plus ends to invade the overlap zone where outward ipMT sliding occurs; and (ii) ipMT depolymerization at the poles ceases, turning MTs flux “off” and tipping the balance of forces to allow outward ipMT sliding to push apart the spindle poles [6-8].

My work will focus on investigating, at ultrastructural resolution, the reorganization of MTs and mitotic spindle components during anaphase B spindle elongation in Drosophila embryos. I am also interest in the regulatory steps that control the ipMTs length.