Ewch i’r prif gynnwys
Veronica Grieneisen

Dr Veronica Grieneisen

Darllenydd

Ysgol y Biowyddorau

Email
GrieneisenV@caerdydd.ac.uk
Telephone
+44 29208 76898
Campuses
Adeilad Syr Martin Evans, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
Users
Ar gael fel goruchwyliwr ôl-raddedig

Trosolwyg

My overarching goal is to unravel the origin and impact of cell and tissue polarity in developing organisms. My strategy has been to compare, contrast and test mechanisms linked to polarity and pattern formation, with inspiration derived from a wider set of systems within both the plant and the animal kingdom.
Research in a nutshell: 
My lab therefore combines molecular biology to biophysics and dynamical systems theory. This means that we are constantly developing and using different approaches, integrating microscopy and image analysis to mathematical models and computer simulations. It also means our lab enjoys working closely with wonderful collaborators of different “fields”, from plant physiology to engineering.
I am particularly drawn to understand how multicellular systems process complex environmental information to make distinct developmental and physiological decisions – which I believe requires a deep understanding of the principles of polar information transport as an integrating element of such signal processing. Therefore, we also intensely explore the role of polarity in the adaptive physiological and developmental changes of plants to their environments.
For a brief overview of my general research philosophy, have a read of our opinion about Causation in Biology, written together with colleagues from different fields.
And here, a BBC4 interview by Philip Ball, in which I talk about the passion and open questions driving my science, in homenage to the centenary of the publication D'Arcy Thompson's "On Growth and Form".
Beyond the Lab:
  • I am delighted to lead the GW4 Community  on "Plasticity and Robustness: cellular understanding of plant growth and defence", with Alan Champneys (Bristol Lead), Kit Yate (Bath Lead) and Mike Deeks (Exeter Lead), which involves an amazing community of plant scientists and mathematical modellers. For more info on our projects, please contact me or Geraint Parry, our GW4 scientific facilitator.
  • Our research engages strongly across the different schools within the Research Theme: Developmental and Regenerative Biology

Cyhoeddiad

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Articles

Ymchwil

What we do:
(I) Map the biophysical implications of established cell and tissue polarity on developmental processes, such as stem cell niche maintenance;
(II) Explore the actual mechanisms that underlie the emergence of cell polarity and the coordination of tissue polarity, which also requires us to zoom out, linking different multicellular evolved systems, plants and animals;
(III) Quantify spatiotemporal constraints acting upon polarised tissue, at the level of gene and protein regulation, such as transporter dynamics in plant nutrient homeostasis.

I. Implications of cell and tissue polarity

From morphogen maximum to minimum

We discovered that associated with the developmentally instructive auxin maximum at the root tip [Nature, 2007] there is a well-defined and tightly controlled auxin minimum positioned more proximally [PLoS Biology, 2008]. Later, we proved that this minimum, and its associated second derivative, is also developmentally instructive in determining the boundary transition between dividing and differentiating cells. We established the biophysical and genetic base of how another important phytohormone, cytokinin, is able to control and position this minimum [PNAS, 2017]. Interestingly, such cytokinin-auxin feedbacks also kick-start the developmental process of nodulation, as found in medicago -- by, again, initiating an auxin maximum [Current Biology, 2019]
Also in other organs auxin can acts as a 'morphogen'. Indeed,  we recently uncovered the mechanism by which another minimum -- in the developing fruit -- is formed, through high transversal fluxes across the minimum region [Molecular Plant, 2019]. The fact that in two different systems these minima have been found, calls for a re-evaluation of the prevailing dogma that boundaries within tissues arise due to positional information read as absolute morphogen thresholds (such as in the classical Wolpert's French Flag concept). This is done by acknowledging that local relative features – such as the spatial curvature in the concentration profile – can be biologically a more reliable and robust way to establish tissue boundaries, and that (high/low) concentrations and (high/low) fluxes can be decoupled.

North, South & East, West: An orthonormal polarity system?

My lab's expertise in modelling polar auxin transport has allowed us to also tackle other important systems in which polar transport through multicellular structures occurs. Many nutrient transporters are polarly localised, such as those for boron, zinc, and magnesium. In plant roots, these are often localised perpendicularly to auxin transporters. This caught my interest some years ago, as it indicated that multiple polarity axes can coexist simultaneously within the same tissue and cells; it remains unclear, however, if they are linked through the same polarity factors (giving different directions, such as N, S, W, E in one compass) or operate independently (alike having two "compasses" in one cell).
We therefore started to model nutrient transport systems in conjunction with our ongoing research on phytohomrone transport. Our work, developed in close collaboration with a leader in plant nutrition, Toru Fujiwara, University of Tokyo, surprisingly predicted confinement of boron in the root tip region, in contrast to the text-book view that the root tip functions principally as an entry point for nutrient uptake. To test these unexpected patterns we transferred an experimental technique (Laser Ablation Inductively Coupled Plasma Mass Spectrometry) to live plant tissues. It provides us with cellular-resolution element measurements, confirming and challenging predicted boron patterning [Plant Cell Physiology, 2015]. With this novel experimental methodology now consolidated and established, we can verify transport models linked to nutrient uptake to other elements, such as zinc, copper and iron. Importantly, this line of investigation cross-talks with our cell-biological work on how polarity and tissue growth are regulated and intertwined, given that environmental factors such as nutrient availability directly impact the way phytohormones are redistributed.

II. The mechanisms that underlie cell and tissue polarity

A new conceptual framework for cell and tissue polarity

Integrating insights from both plant and animal research, in collaboration with the Marée Lab here in Cardiff,  the Coen lab at JIC and Leah Keshet, from UBC, allowed us to develop a novel conceptual framework to understand the establishment of tissue cell polarity. In contrast to previous models, we propose that a fundamental building block for tissue cell polarity is the process of establishment of individual cell polarity in the absence of asymmetric cues. Coordination of polarities then arises through cell-cell coupling, which can operate directly in animals, through membrane-spanning complexes, or indirectly in plants, through diffusible molecules [Development, 2013]. Starting from such generalised concepts, my lab wishes to unravel the actual molecular players involved. We have proposed a mechanism which could be a strong candidate for spontaneous intracellular partitioning in both plants and animals, involving the highly conserved biochemistry of small G-proteins. We have shown how due to such biochemistry spontaneous polarisation can occur and be lost, taking into account that processes take place in an inherently variable and noisy environment [Bulletin of Mathemacial Biology, 2012]. Moreover, we have shown the importance of taking cell shape dynamics into account, and in order to get a much more complete picture of the key cell polarity determinants in both animal and plant systems we had to dive much deeper into the biochemistry and biophysics [PloS Computational Biology, 2012]. This base allowed us to study the similarities and differences in cell polarity for diverse systems such as the plant gynoecium [Journal of Integrative Plant Biology, 2013] and moving keratocytes [Bulletin of Mathemacial Biology, 2006, PloS Computational Biology, 2012]. These studies rest at the core interest of the lab, given that they involve fundamental processes of protein redistribution and patterning, linking biochemistry to the biophysics of cell shape and tissue organisation.

A cellular jigsaw puzzle

To probe polarity communication, the Grieneisen Lab has set up an integrative modelling-experimental approach, choosing the leaf epidermal pavement cells as our paradigm system. These cells, already highlighted by D'Arcy Thompson as a misfit with respect to surface-tension minimisation, undergo fascinating shape changes, to become alike jigsaw puzzle pieces with many lobes and indentations, perfectly interlocking with their cellular neighbours. To link cell tracking experiments to modelling my lab has developed novel shape analysis techniques, based on a modification of Elliptic Fourier Analysis [Development, 2018], as well as a new cell segmentation, tracking and analysis pipeline [Development, 2017]. Each lobe and indentation can be considered an individual polarised structure, so these cells exhibit highly organised, multiple polarities. The pattern, however, should not be seen as a simple, downstream effect of polarising signals, but instead involves feedbacks between cell shape and patterning of each individual cell and the cell-cell signalling and bio-mechanical coupling between the neighbouring cells, and are coordinated in a organ-level fasion [PloS Biology, 2018]. To unravel such complexity, an integrated systems biology approach is required. We have developed advanced computational modelling techniques [Magno 15], mathematical and bioinformatic analysis, and experimental approaches to address this ongoing pavement cell puzzle.

III. Spatio-temporal constraints acting upon polarised tissue

Why has a developmental mechanism been selected?

Our research has shown many examples of how plants exploit cell and tissue polarity to generate self-renewable gradients on a fast time-scale that are sufficiently informative and robust to guide tissue growth [Nature, 2007]. But such studies do not immediately explain why plants use complex implementations of directed auxin transport, such as the reflux-loop. By performing comparative model studies in which different mechanisms of gradient establishment were analysed side-by-side, it became clear that although other mechanisms were perfectly able to generate the same steady state gradients of similar shape and steepness, they dramatically fell short with respect to their robustness towards fluctuations and variations in biophysical parameters, timescales of pattern establishment and functional communication distances [Grieneisen.bsb12]. In short, our theoretical work revealed that only with a complex, coordinated and structured tissue layout the plant is able to concomitantly deal with the temporal and spatial patterning requirements of a growing tissue.

Polarised tissues and traffic jams

Such constraints are also present for nutrient fluxes. While studying the boron dynamics through the roots, we noticed an apparent paradox, namely that while soil boron concentrations present only small variations in space and time, their corresponding transporter regulation is in contrast very fast, adapting to thousandfold changes in boron concentration within 10 min. Modelling revealed that an efficient homogeneous flow of boron through the cells from the medium into the internal roots tissues (xylem) can only be obtained if response times of these transporters to the intracellular boron concentration (which regulates the transport levels) is sufficiently rapid. Otherwise nutrient throughput becomes inherently unstable and suffers “traffic jam” behaviour, with suboptimal xylem loading combined with high and oscillatory back-propagating peaks of toxic boron concentrations through the tissue [Elife, 2017]. These insights can be generalised to any polarly transported substance that has a direct feedback on the transporters themselves, and constitute yet another unexpected constraint acting upon polarised tissue.

Addysgu

Undergraduate teaching at Cardiff University: 

  • BI3157: Systems Biology: dynamical systems and simulations of biological systems.
  • BI3156: Systems Biology and Modelling: introducing undergraduate students to dynamical systems and simulations of biological systems.
  • BI3252: Omics revolution: `Morphomics' teaching how to employ R-scripts and principles of shape analysis to effeciently retrieve meaningful morphometrics from imaging data, and to then process such high-throughput data analysis to gain biological insights and ask new questions.
  • BI3252: Resistance to drought changes: practical on plant responses to drought, genetics, stomata biology.
  • BI1004: The Dynamic Cell: ‘Applied Cell Biology and Imaging’. showcasing the usage of systems biology for understanding the complex behaviour and shapes of cells.
  • BI1001: Skills for Science: hands-on lab work.
  • BI3001: Biosciences Final Year Project. Menoring students on a range of research projects in morphogenesis and systems biology. 

Other past teaching rolls: 

  • Honorary Lecturer at the School of Biological Sciences, UEA. 2018.
  • External Lecturer of several plant science courses at UEA. 2014–2016.
  • Co-Organiser and instructor of and developer of teaching material for the EMBO “Multi-level Modelling of Morphogenesis” course, held 5 times (2010, 2011, 2013, 2015, 2017). 
    • Public: 28 selected PhD students, postdocs and junior group leaders.
  • Teacher of the BBSRC DTP Systems Biology training programme, at the JIC, Norwich, UK, in spring 2013, 2014, 2015, 2016, 2017 and 2018:
    • Obligatory lectures and hands-on exercises for all DTP (Doctoral Training Programme) students across the Norwich Research Park (including the University of East Anglia).
    • Involved teaching essential mathematical and systems biology skills to biology PhD students. Besides lectures and course material, we developed computer exercises to promote interactive learning.
    • Topics I have taught:
      • Modelling genetic regulatory networks, a dynamical systems approach.
      • General introduction to Ordinary Differential Equations and Partial Differential Equations.
      • Gene regulatory networks and Boolean logic.
      • How to analysis and model cell shape.
  • Teacher at the Oxford Brookes University Eco-Evo-Devo Summer School. Oxford, UK, 8–10/8/2016.
  • “Lunch and Learning” session with the sixth form girls from the Norwich High School for Girls, “Self-Organisation in biological development: how computational sciences, mathematics and physics (and robots!) can help us understand how organisms make themselves”, 28/1/2015.
  • Keynote Speaker at the The 8th Scandinavian Plant Physiology Society PhD Students Conference, Uppsala, Sweden, 16–1962014.
  • Instructor/Speaker at the 3rd Summer School in Evolutionary Developmental Biology, Conceptual and Methodological Foundations, held by the Instituto Veneto di Scienze, Lettere ed Arti, “From gene networks to organismal systems”, Venice, Italy, 23–27/9/2013.
  • Teacher at the first Systems Biology Summer Course at the Centre for Genomic Regulation (CRG), Barcelona, Spain, 4–8/7/2011.

Bywgraffiad

Trwy gydol fy mywyd rwyf wedi bod yn aficionado o systemau cymhleth addasol. Ar ôl cael fy ngradd Baglor mewn Ffiseg a Meistr mewn Ffiseg Ddamcaniaethol (o'r Universidade Federal do Rio Grande do Sul, yn fy nhref enedigol Porto Alegre, Brasil) roeddwn yn arbenigo yn ystod ac ar ôl fy astudiaethau graddedig mewn ymchwil bioffisegol a rhyngddisgyblaethol. Derbyniais fy PhD, mewn Bioleg Ddamcaniaethol, cum laude o Brifysgol Utrecht. Yno yn ystod fy astudiaethau graddedig y dechreuais gymhwyso systemau a dulliau rhagfynegol o broblemau datblygiad biolegol wrth integreiddio modelau ac arbrofion yn agos.   Yn dilyn fy PhD (a thaith i'r Amazon) dechreuais fy labordy fy hun yng Nghanolfan John Innes ar unwaith, gan arwain tîm rhyngddisgyblaethol o ffisegwyr, mathemategwyr a biolegwyr. Yna symudais i Brifysgol Caerdydd ddiwedd 2018, lle mae gen i'r pleser aruthrol o weithio mewn amgylchedd gwyddonol ac academaidd cyfoethog ac amrywiol iawn.
  • PhD cum laude mewn Bioleg Ddamcaniaethol. 27 Awst 2009 o Brifysgol Utrecht, yr Iseldiroedd. Goruchwyliwr: Paulien Hogeweg. Cyd-oruchwyliwr: Ben Scheres
    • Title: "Dynameg patrymu auxin mewn morffogenesis planhigion"
  • Meistr mewn Ffiseg Ddamcaniaethol. 9 Tachwedd 2004. (UFRGS), Porto Alegre, Brasil. Goruchwyliwr: Rita M.C.  de Almeida
    • Teitl: "Dinâmica do estabelecimento de configurações em estruturas cellulares".
      Cyfieithiad: "Dynameg patrymau mewn strwythurau cellog".
      Uchafswm gradd â sgôr, rheithgor amddiffyn dan arweiniad yr Athro Herch Moysés Nussenzveig.
  • Baglor mewn Gwyddoniaeth mewn Ffiseg. 1 Chwefror 2001. O'r Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brasil.

Anrhydeddau a dyfarniadau

  • Cymrodoriaeth Dorothy Hodgkin y Gymdeithas Frenhinol, 2009–2014.
  • Medal Llywydd Cymdeithas Bioleg Arbrofol, 2011.
  • Gwobr Hugo de Vries, 2009.

Aelodaethau proffesiynol

  • Associate Theme Lead for the Cardiff University Theme "Developmental and Regenerative Biology". Current.
  • Nominated Member of the International Scientific Advisory Board of the Saclay Plant Science (SPS) Network, France, 2018–2027.
  • Royal Society Dorothy Hodgkin Fellow, 2009–2014.
  • Member of the Society of Mathematical Biology, since 2011.
  • Member of the Society for Experimental Biology, since 2011.
  • Member of Nederlandse Vereniging voor Theoretische Biologie, 2005-2018.

Safleoedd academaidd blaenorol

  • 2019-cyfredol: Darllenydd, Prifysgol Caerdydd
  • 2009-2018: Arweinydd y grŵp, Canolfan John Innes
    • Sefydlodd Lab Grieneisen ar 01-10-2009.
  • 2017-presennol: Darlithydd Anrhydeddus yn Ysgol y Gwyddorau Biolegol, UEA.
  • 2009-2014: Cymrawd Prifysgol y Gymdeithas Frenhinol yn yr UEA, Ysgol Bioleg Prifysgol East Anglia

Pwyllgorau ac adolygu

  • Bwrdd Cynghori Golygyddol,  Yn Silico Plant Journal.
  • Adolygydd Journal o gyfnodolion amrywiol
  • Adolygydd Grant, BBSRC; ANR, ERC, ac ati

Meysydd goruchwyliaeth

Work on plant modelling is ongoing with PhD Eleanor Harold-Barry and Toby Boyacigiller.

My lab is also hosting several undergraduate students.

I am interested in supervising PhD students in the areas of:

  • Systems Biology
  • Cell and Developmental Biology
  • Morhodynamics (biological as well as computational/mathematical)
  • Plant Morphogenesis and Physiology
  • Evo-Devo of multicellularity
  • Imaging Analysis
  • Morpho-Robotics

Ymgysylltu

Array

External profiles