Professor Marysia Placzek

Marysia Placzek

Professor in Developmental Neurobiology
Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: D18b Firth Court
Telephone: +44 (0) 114 222 2353
Email: m.placzek@sheffield.ac.uk

Patterning & Morphogenesis Bateson Centre


NeuroscienceStem Cells and Regenerative Medicine


Developmental Biology

General

Brief career history

  • 2014-2015 Director of the Bateson Centre (formerly, The MRC Centre for Developmental and Biomedical Genetics) at the University of Sheffield .
  • 2009-2014 Acting Director, MRC Centre for Developmental and Biomedical Genetics
  • 2007-2009 Deputy Director, MRC Centre for Developmental and Biomedical Genetics
  • 1999-present: Professor in Developmental Neurobiology, University of Sheffield.
  • 1997-1999: Senior Lecturer, University of Sheffield.
  • 1992-1997: Scientific Staff, National Institute of Medical Research, London.
  • 1983-1987: Post-doctoral fellow, Columbia University, New York. Research Advisor: Dr Jane Dodd.
  • 1983-1987: PhD. Imperial Cancer Research Fund and Imperial College, London. Research Advisor: Dr Gordon Peters.
  • 1979-1983: Bsc, University of Edinburgh.

Research interests

We study how the hypothalamus of the brain is formed in the embryo

In development,  hypothalamic nerves and glia are built in space and time with an order and precision that leads ultimately to the integrated assembly of the brain-body axis. The proper development of the hypothalamus is therefore vital to ensure that throughout life, brain and body function in perfect harmony and balance. Our research focuses on the stem and progenitor cells that build the hypothalamus. Our goal is to characterise the molecular networks involved in hypothalamic development, and determine how they work to build and maintain the different cells of the hypothalamus. Our work will contribute to understanding the importance of the hypothalamus to robust long-term health and will shed light onto diseases and disruptions of homeostasis.

Professional activities

  • Scientific Advisory Board member Roslin Institute (2008-2011)
  • 2012: MRC Suffrage Science Heirloom Recipient
  • 2013-present: External Examiner, Dept. Zoology Cambridge
  • 2015: MRC Doctoral Training Partnership Panel Member

Full publications

Research

Building the hypothalamus through life

My research focuses on the development of the hypothalamus and on its cellular plasticity over the lifecourse.

The functions of the hypothalamus in mediating homeostasis are well-known. By contrast, little is understood of how hypothalamic cells form in development. This knowledge is important, because early indications suggest that deregulation of developmental programmes may underlie complex human pathological conditions, including stress and eating disorders. Our goal is therefore to understand how the hypothalamus develops in the embryo and how the proper embryonic assembly of the hypothalamus holds the key to robust adult function. We focus in particular on five key areas:

  • The role of the prechordal mesoderm and the importance of its dynamic cellular and signalling properties to induction of a multipotent embryonic hypothalamic progenitor.
  • The characterisation of the multipotent embryonic hypothalamic progenitor, in particular identification of the molecular and cellular cues that maintain a multipotent hypothalamic progenitor, or that promote its differentiation to different sets of hypothalamic neurons and glia, including infundibular glia.
  • The cellular and molecular events that underlie the integrated assembly of the hypothalamo-pituitary neuraxis.
  • The characterization of stem/progenitor-like tanycytes in the adult hypothalamus
  • The importance of appropriate hypothalamic assembly to the stress-regulatory pathway and robust adult behaviour and health.

We use a range of animal model systems (chick, mouse, zebrafish) and combine in vivo and ex vivo approaches with imaging, transgenic, gain-and loss-of-function approaches to characterise how stem/progenitor cells renew, or differentiate in response to local and systemic signals.

Figure 1

Funding

Teaching

Undergraduate and postgraduate taught modules

Level 2:

  • BMS236 Building Nervous Systems

Level 3:

  • BMS326 Modelling Human Disease (Coordinator)
  • BMS351 Gametes, Embryos and Stem Cells
  • BMS381 Developmental Neurobiology
  • BMS339 Patients as Educators Project
  • BMS349 Extended Library Project
  • BMS369 Laboratory Research Project

Masters (MSc):

  • BMS6055 Modelling Human Disease (Coordinator)
  • BMS6351 Gametes, Embryos and Stem Cells
Opportunities

Postgraduate PhD project

Understanding hypothalamus self-assembly through experiment and simulation

Supervisors: Professor Marysia Placzek (BMS) and Dr Alexander Fletcher (Maths)

Funding status: A four-year fully funded EPSRC studentship is available to home students starting in October 2018.

See also

Background

An exciting PhD project in developmental neurobiology is available at the University of Sheffield under the supervision of Dr Alexander Fletcher and Prof. Marysia Placzek. This project is on the development of the hypothalamus, a brain structure with very similar anatomy across vertebrate species. We know that the hypothalamus is very important for mediating physiological homeostasis, yet its development remains poorly understood. This project, a collaboration between researchers in the Department of Biomedical Sciences (the Placzek lab) and the School of Mathematics and Statistics (the Fletcher group), will address how this important structure is formed during development.

The Placzek lab recently showed that the basal hypothalamus self-assembles in vivo from a FGF10+ stem-like population. This population gives rise to a progenitor cell population that grows outward and transiently expresses Shh [1]. Once set up, both Ffgf10+ and Shh+ cell populations are maintained throughout embryogenesis and keep producing the progenitor cells that are needed to develop the neurons in the hypothalamus [2]. Surprisingly, when cultured in vitro, the FGF10+ population grows into an organoid-like structure that closely resembles the hypothalamus in vivo. This suggests that these stem-like cells work autonomously and can self-organise into the basal hypothalamus. We do not yet know how the hypothalamus self-assembles, and how the correct balance of stem, progenitor and differentiated cells is established and maintained, but we do know that Shh signalling is required [3]. Intriguingly, Shh operates both as a long-range morphogen that patterns tissues and a short-range signal that selects progenitor cells [4] to mediate cellular homeostasis and self-organisation, but how this occurs is not known.

To address this conundrum, this project will combine experiments and computational modelling. Experimentally, you will use the chick embryo, whose relatively large size allows us to perform assays with precise temporal and spatial control to determine the coupling of patterning, growth and morphogenesis, and where we have tools available to distinguish between short- and long-range signalling mediated by Shh. You will perform gain-and loss-of function studies in vivo and ex vivo 3D culture, and use computational modelling [5] to interpret these experimental observations and test sufficiency of hypothesised mechanisms.

This project is a great opportunity for a neuroscience student interested in developmental neurobiology, who is keen to tackle new techniques and work in a truly interdisciplinary environment. You will acquire programming and modelling skills and gain expertise in tissue culture and imaging. The project provides a real opportunity to advance the state-of-the-art in modelling tissue self-assembly, and reveal how a stem cell can build an organoid in vitro that closely resembles its in vivo counterpart, the holy grail of tissue engineering and regenerative medicine.

References

  1. Fu et al (2017). Fgf10+ progenitors give rise to the chick hypothalamus by rostral and caudal growth and differentiation. Development. 144:3278-88.
  2. Robins et al (2013). α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun. 4:2049.
  3. Carreno et al (2017). Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors. Development. 144:3289-302.
  4. Muthu et al (2016). Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus. Development. 143:2651-63.
  5. Fletcher et al (2017). Mechanocellular models of epithelial morphogenesis. Phil Trans R Soc B. 372.

Contact information

For informal enquiries about the project or application process, please feel free to contact me, or:

For further information about this project and how to apply, see our PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles