Combining quantitative experiments and theory to understand the architecture and dynamics of self-organizing, subcellular structures, particularly the metaphase spindle.
NorthWest Building, Room 365.10
52 Oxford Street
Cambridge, MA 02138
Lab Size: Between 5 and 10
The Needleman laboratory combines quantitative experiments and theory to study the architecture and dynamics of self-organizing subcellular structures. We presently focus on trying to understand the cell division and spindle assembly and function. Research in the group can be divided into three broad categories: spindle biophysics, spindle physics, and spindle evolutionary biology. This work is highly interdisciplinary and combines approaches from engineering, physics, and biology.
Spindle Biophysics:Spindles are composed of microtubules and associated proteins. It is unclear how the activity of microtubules gives rise to the spindle, largely because we do not know how microtubules act in spindles. We are using quantitative measurements, theory, and computer simulation to determine how microtubules behave in spindles in human cells. This project entails extensive technique development. The ultimate goal of this work is to create mesoscopic models that can predict the response of the spindle to disease state and novel therapeutic drugs.
Spindle Physics: Spindles can be composed of hundreds of thousands of microtubules, whose collective interactions are ultimately responsible for biological behaviors. We are testing field theoretic models of spindles in Xenopus egg extracts to gain insight into these collective effects. We are exploring these spindle’s structure, dynamics, and response to perturbations. Our approach is inspired by methods successfully used in soft condensed matter physics.
Spindle Evolutionary Biology:Spindles in different organisms and different tissues within organisms are different, but very little is known about the mechanistic reasons for these differences or the evolutionary forces ultimately responsible for them. We are address these issues using biophysical, quantitative genetic, and comparative approaches on spindles in early nematode embryos.
Foster PJ, Fürthauer S, Shelley MJ, Needleman DJ. Active contraction of microtubule networks. eLife. 2015 :10.7554/eLife.10837
Farhadifar R, Baer CF, Valfort A-C, Andersen EC, Müller-Reichert T, Delattre M, Needleman DJ. Scaling, selection, and evolutionary dynamics of the mitotic spindle. Current Biology. 2015;25 :732–740
Brugués J, Needleman D. Physical basis of spindle self-organization. Proceedings of the National Academy of Sciences. 2014;111 :18496–18500
Yu C-H, Langowitz N, Wu H-Y, Brugues J, Needleman D. Measuring Microtubule Polarity in Spindles with Second-Harmonic-Generation Microscopy. Biophysical Journal. 2014;106 :1578-1587
Brugués J, Nuzzo V, Mazur E, Needleman DJ. Nucleation and transport organize microtubules in metaphase spindles. Cell. 2012;149 :554–564