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

Bateson Centre


Neuroscience


Stem Cells and Regenerative Medicine

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

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