I am biophysicist trained biologist trying to unravel the mysteries hidden in the living matter through a combination of biology, microscopy and physics. In the past I worked on chloride channels of parasites via electrophysiology , single molecule force spectroscopy via atomic force microscopy, and intracellular forces associated to the mitotic spindle via magnetic tweezers. Currently, I focus on mechano-sensing and mechano-transduction aiming to understand the pathways that transmit and transform force cues into molecular signals in cells and tissues.
Honors & Awards
HFSP Fellowship, HFSPO (2017-2020)
Springboard-to-postdoc fellowship, DIPP (2015)
Fellowship for master studies, DAAD (2008)
Postdoc, Dunn Lab - Stanford University (2016)
Short-Postdoc, Brugues Lab - Max Planck Institute of Molecular Cell Biology and Genetics (2015)
Doctor of Philosophy, Technische Universitat Dresden (2015)
PhD thesis, Howard Lab - Max Planck Institute of Molecular Cell Biology and Genetics
Master of Science, Technische Universitat Dresden (2010)
Master thesis, Muller lab - ETH Zürich - Department of Biosystems Science and Engineering
Diploma, Universidad Nacional De Colombia (2008)
Diploma thesis, Stuhmer Lab - Max Planck Institute of Experimental Medicine
Alexander Dunn, Postdoctoral Faculty Sponsor
A force-generating machinery maintains the spindle at the cell center during mitosis.
Science (New York, N.Y.)
2016; 352 (6289): 1124–27
The position and orientation of the mitotic spindle is precisely regulated to ensure the accurate partition of the cytoplasm between daughter cells and the correct localization of the daughters within growing tissue. Using magnetic tweezers to perturb the position of the spindle in intact cells, we discovered a force-generating machinery that maintains the spindle at the cell center during metaphase and anaphase in one- and two-cell Caenorhabditis elegans embryos. The forces increase with the number of microtubules and are larger in smaller cells. The machinery is rigid enough to suppress thermal fluctuations to ensure precise localization of the mitotic spindle, yet compliant enough to allow molecular force generators to fine-tune the position of the mitotic spindle to facilitate asymmetric division.
View details for DOI 10.1126/science.aad9745
View details for PubMedID 27230381
Stars take centre stage
View details for DOI 10.1038/s41567-018-0164-2
Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces: Mechanics of mitotic spindle positioning.
BioEssays : news and reviews in molecular, cellular and developmental biology
2017; 39 (11)
Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against- the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells.
View details for PubMedID 28960439
View details for PubMedCentralID PMC5698852
The Mitotic Spindle in the One-Cell C. elegans Embryo Is Positioned with High Precision and Stability.
2016; 111 (8): 1773-1784
Precise positioning of the mitotic spindle is important for specifying the plane of cell division, which in turn determines how the cytoplasmic contents of the mother cell are partitioned into the daughter cells, and how the daughters are positioned within the tissue. During metaphase in the early Caenorhabditis elegans embryo, the spindle is aligned and centered on the anterior-posterior axis by a microtubule-dependent machinery that exerts restoring forces when the spindle is displaced from the center. To investigate the accuracy and stability of centering, we tracked the position and orientation of the mitotic spindle during the first cell division with high temporal and spatial resolution. We found that the precision is remarkably high: the cell-to-cell variation in the transverse position of the center of the spindle during metaphase, as measured by the standard deviation, was only 1.5% of the length of the short axis of the cell. Spindle position is also very stable: the standard deviation of the fluctuations in transverse spindle position during metaphase was only 0.5% of the short axis of the cell. Assuming that stability is limited by fluctuations in the number of independent motor elements such as microtubules or dyneins underlying the centering machinery, we infer that the number is ∼1000, consistent with the several thousand of astral microtubules in these cells. Astral microtubules grow out from the two spindle poles, make contact with the cell cortex, and then shrink back shortly thereafter. The high stability of centering can be accounted for quantitatively if, while making contact with the cortex, the astral microtubules buckle as they exert compressive, pushing forces. We thus propose that the large number of microtubules in the asters provides a highly precise mechanism for positioning the spindle during metaphase while assembly is completed before the onset of anaphase.
View details for DOI 10.1016/j.bpj.2016.09.007
View details for PubMedID 27760363
The Transmembrane Protein KpOmpA Anchoring the Outer Membrane of Klebsiella pneumoniae Unfolds and Refolds in Response to Tensile Load
2012; 20 (1): 121-127
In Klebsiella pneumoniae the transmembrane β-barrel forming outer membrane protein KpOmpA mediates adhesion to a wide range of immune effector cells, thereby promoting respiratory tract and urinary infections. As major transmembrane protein OmpA stabilizes Gram-negative bacteria by anchoring their outer membrane to the peptidoglycan layer. Adhesion, osmotic pressure, hydrodynamic flow, and structural deformation apply mechanical stress to the bacterium. This stress can generate tensile load to the peptidoglycan-binding domain (PGBD) of KpOmpA. To investigate how KpOmpA reacts to mechanical stress, we applied a tensile load to the PGBD and observed a detailed unfolding pathway of the transmembrane β-barrel. Each step of the unfolding pathway extended the polypeptide connecting the bacterial outer membrane to the peptidoglycan layer and absorbed mechanical energy. After relieving the tensile load, KpOmpA reversibly refolded back into the membrane. These results suggest that bacteria may reversibly unfold transmembrane proteins in response to mechanical stress.
View details for DOI 10.1016/j.str.2011.11.002
View details for Web of Science ID 000299195600013
View details for PubMedID 22244761