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

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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

A major focus of our research is to understand the development of the vertebrate hypothalamus. We are aiming to characterise the signalling factor/transcription factor networks that mediate hypothalamic development, elucidate how hypothalamic stem cells progress into defined neuronal cells and how their axons project to different components of the hypothalamus. A second focus is the elucidation of the signalling factor/transcriptional networks that underlie development of the prechordal mesoderm.

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 its resident cells form in development, or through life. This knowledge is important, because early indications suggest that deregulation of developmental programmes may underlie complex human pathological conditions, including stress and eating disorders. 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.

Recent work has focused on FGF signalling, showing its importance in building brain-body interfaces (1) and in the proliferation of resident stem/progenitor cells in the embryo (2) and adult (3). Currently we are examining other signalling pathways that promote differentiation, and collaborating with Towers to address the role of cell cycle in hypothalamic morphogenesis. With Furley, we are further characterising hypothalamic neural stem/progenitor cells and the local factors, including cell adhesion molecules, that govern their behaviour.

A role for glucocorticoids in stimulating neurogenesis from adult hypothalamic stem cells (3) is being investigated with Taylor (University of Basel), while with Cunliffe, Watt and Wood (UoS) we ask whether alterations in hypothalamic stem/progenitor cell behaviour underlie pathological conditions. In collaboration with Lovell-Badge (Crick Institute, Mill Hill) we are examining if hypothalamic stem cells decline in ageing, with consequences on neuronal depletion.

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

Functional characterisation of stem cell-derived neural progenitors in the central nervous system

Co-supervisor: Dr Anestis Tsakiridis

Human pluripotent stem cells (hPSCs) are a valuable source of clinically relevant cell populations such as neural progenitors and neurons (Suzuki and Vanderhaeghen, 2015). However, conventional differentiation protocols produce predominantly neural cell types corresponding to the anterior central nervous system (CNS) such as the brain and anterior (cervical) spinal cord but fail to generate efficiently more posterior (thoracic/lumbosacral) spinal cord cells. In vivo, the anterior-posterior (A-P) identity of various CNS cell types has been shown to influence both their function and their susceptibility to neurodegeneration e.g. in the case of Amyotrophic lateral sclerosis (ALS).

Currently it is unknown whether such differences exist in in vitro-derived neural cells and whether the predominantly anterior CNS cell types generated from hPSCs are functionally equivalent to their posterior counterparts. This is an important issue for the design of drug screening/disease modelling experiments as well as cell replacement-based therapies that employ neural derivatives of hPSCs. We have recently described the in vitro generation of neuromesodermal progenitors (NMPs), the bona fide early precursors of spinal cord in vertebrate embryos, from hPSCs (Henrique et al. 2015; Gouti et al., 2015). Using NMPs as the starting population we have now established pilot protocols driving the robust induction of posterior spinal cord progenitors and neurons in vitro.

The proposed PhD project combines expertise in the Tsakiridis and Placzek labs in the derivation and manipulation of stem cells (Gouti et al. 2015; Robins et al. 2013) and aims to examine whether posterior CNS cells “behave” in the same way as their anterior counterparts in terms of:

1) Vulnerability to excitotoxicity/cellular stress
2) Ability to contribute to normal CNS development
3) Capacity to mediate regeneration

The project will employ a variety of experimental approaches such as hPSC culture and differentiation, high content imaging and chick embryo manipulation.

References

1) Suzuki IK and Vanderhaeghen P Development. 2015 Sep 15;142(18):3138-50).
2) Henrique D et al. Development. 2015 Sep 1;142(17):2864-75.
3) Gouti M et al. PLoS Biol. 2014 Aug 26;12(8):e1001937.
4) Robins SC et al. Nat Commun. 2013;4:2049.

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

PhD Opportunities

Selected publications

Journal articles