Adjunct Associate Professor
- Senior Principal Investigator, IMCB, A*STAR.
- Associate Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
- HHMI International Scholar.
- EMBO Young Investigator.
Nicolas studied biology at the University of Buenos Aires (Argentina) and University of Tel-Aviv (Israel). He did his PhD with Yves-Alain Barde at the Biozentrum (University of Basel, Switzerland) and postdoc in biological imaging with Scott Fraser at Caltech (US), supported by fellowships from Swiss National Foundation, EMBO and CIRM. He was appointed Group Leader at EMBL Australia in 2011 and joined A*STAR in 2015 as Senior PI. He received the A*STAR Investigatorship, Viertel Medical Fellowship, Australian NHMRC and ARC Fellowships. In 2015 he become the third Singapore-based scientist to join the EMBO Young Investigator Program. In 2016 he was awarded the Gibco–Emerging Leader Prize of the American Society for Cell Biology (ASCB). In 2017 he became an HHMI International Scholar.
Cell & developmental biology, imaging, neurosciences, biophysics.
Lab Website: imcb.a-star.edu.sg/php/np.php
Imaging how cells decide their fate, shape and position in the living mammalian embryo
During development, each cell in our body must resolve its fate, shape and position. Revealing how these decisions are made is critical to understand how embryos form, and what problems compromise fertility, yet their real time control in mammals is unknown. Because fixed specimens cannot capture in vivo cell dynamics, we apply advanced imaging technologies to study cells directly in live mouse embryos.
We recently provided the first biophysical explanation of how transcription factors (TFs) search and bind on-and-off to DNA to control cell fates in vivo. Combining fluorescence correlation spectroscopy with photo-activation (paFCS), we showed how the dynamics of Sox2 and Oct4 control pluripotency at the single-cell level in the embryo (White et al 2016 Cell; Kaur et al 2013 Nat. Comms.; Zhao et al 2017 Nat. Prot.).
Using live imaging, we also discovered that cells use a new class of long filopodia to form the first tissue-like structures of the embryo. These protrusions enable cells to draw their neighbours closer and achieve embryo compaction, providing a new picture of how mammalian cells form epithelial structures in vivo (Fierro-Gonzalez et al 2013, Nat. Cell Biol.).
We also established computer segmentation and laser ablation techniques to demonstrate that anisotropies in cortical tension (a force generated by contractility of the cell cortex) drive the formation of the pluripotent inner mass of the embryo. Our findings challenged models based on spatially orientated divisions and established a role for mechanical forces in preimplantation development (Samarage et al 2015, Dev. Cell).
Recently, we explored the dynamics of microtubules in vivo. The microtubules of most animal cells are organized by an organelle called the centrosome. Using live imaging in the early mouse embryo, which lacks centrosomes, we revealed that the cells are connected by a stable microtubule bridge. This bridge functions as a non-centrosomal organizing center, directing the growth of microtubules within the cell. Moreover, the microtubules emanating from this bridge transport key proteins to the cell membrane, including E-cadherin, to control cell polarization during development (Zenker et al 2017, Science).
Our discoveries reveal how multiple mechanisms regulating cell fate, shape and position are integrated in vivo to direct the earliest stages of mammalian life. We now extend these studies to more complex morphogenetic processes and other cell types like neurons and stem cells.
- Zenker J, White M, Templin R, Parton R, Thorn-Seshold, Bissiere S, Plachta N.A microtubule organizing center directing intracellular transport in the early mouse embryo. Science(2017)
- Zhao Z, White M, Alvarez Y, Zenker J, Bissiere S, Plachta N.Quantifying transcription factor–DNA binding in single cells in vivo with photoactivatable fluorescence correlation spectroscopy.Nature Protocols( 2017)
- White M, Angiolini J, Alvarez Y, Kaur G, Zhao Z, Moksos E, Bruno L, Bissiere S, Levi, Plachta N.Long-lived binding of Sox2 to DNA predicts cell fate in the four-cell mouse embryo.Cell (2016) [See Preview by Wu & Ispizua-Belmonte]
- Samarage R, White M, Alvarez Y, Fierro-Gonzalez J, Jesudason E, Hanon Y, Fouras A, Plachta N.Cortical tension positions the first inner cells of the mammalian embryo. Developmental Cell (2015) [See Dev Cell Preview by Goldstein & Kiehart, 2015]
- Bouveret R et al.NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets. eLife (2015)
- Angiolini J, Plachta N, Mocskos E, Levi V.Exploring the Dynamics of Cell Processes through Simulations of Fluorescence Microscopy Experiments. Biophysical Journal (2015)
- Fierro-Gonzalez J, White M, Silva J, Plachta N. Cadherin-dependent filopodia control preimplantation embryo compaction. Nature Cell Biology (2013)[2 reviews by Faculty 1000]
- Kaur G, Nefzger C, Costa M, Silva J, Fierro-Gonzalez J, Polo J, Bell T, Plachta N. Probing transcription factor diffusion in the developing mammalian embryo with photoactivatable fluorescence correlation spectroscopy. Nature Communications (2013)
- Plachta N, Bollenbach T, Pease S, Fraser SE, Pantazis P.Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nature Cell Biology (2011)[Journal Cover. See NCB News & Views by Zernicka-Goetz, 2011. 3 reviews by Faculty 1000.]
- Bissiere S, Plachta N, McAllister K, Hoyer D, Olpe HR, Grace A, Cryan JF. The anterior cingulate cortex modulates the efficiency of amygdala dependent fear learning. Biological Psychiatry (2008) (Journal Cover)
- Nikoletopoulou V, Plachta N, Allen ND, Haubst N, Götz M, Barde Y-A. Neurotrophin receptor-mediated death of misspecified neurons generated from embryonic stem cells lacking Pax6. Cell Stem Cell (2007)
- Plachta N, Annaheim C, Bissiere S, Hoving S, Voshol V, Bibel M, Barde Y-A. Identification of a lectin causing the degeneration of neuronal processes using engineered embryonic stem cells. Nature Neuroscience (2007)
- Plachta N, Bibel M, Tucker KL, Barde Y-A. Developmental potential of defined neural progenitors derived from mouse embryonic stem cells. Development (2004)
- Plachta N, Traister A, Weil M. Nitric oxide is involved in establishing the balance between cell cycle progression and cell death in the developing neural tube. Experimental Cell Research (2003)
- Traister A, Abashidze S, Gold V, Plachta N, Karchovsky E, Patel K, Weil M. Evidence that nitric oxide regulates cell cycle progression in the developing chick neuroepithelium. Developmental Dynamics (2002)