Stem cell biology

JUERGEN KNOBLICH AT

Institute of Molecular Biotechnology, Vienna

Modelling human brain development and disease in 3D culture

The huge complexity of our brain develops from a relatively small number of stem and progenitor cells. Our group focuses on the molecular mechanisms that allow stem cells to generate the enormous divergence of cell types we find in the central nervous system. For this, we use the fruit fly Drosophila to identify relevant genes and gain mechanistic insights. We then test functional the conservation of the identified mechanisms in the developing mouse brain. Finally, we have developed a 3D culture system that allows us to model human brain development starting from pluripotent stem cells, a method that ultimately allows us to apply our knowledge to human disease.

Biography

Juergen Knoblich is a senior scientist and deputy director at IMBA. He obtained his PhD from the Max Planck Institute in Tübingen. After a postdoctoral period in the laboratory of Yuh Nung Jan at UCSF, San Francisco, he joined the IMP in 1997 as a junior group-leader. In 2004, he moved to IMBA where he is now senior scientist and deputy director. His research activities are centered around lineage specification and proliferation control in neural stem cells during brain development. Juergen Knoblich’s group has recently established a 3D culture model that allowed them to recapitulate the early development of a human brain in organoid culture starting from patient derived pluripotent stem cells. He is a member of the Austrian Academy of Sciences and the Academia Europea, holds an advanced grant of the European Research Council and has received the Wittgenstein prize, the Schroedinger award of the Austrian Academy of Sciences, the Sir Hans Krebs medal of the Federation of European Biochemical Societies, the EMBO young investigator award, the FEBS anniversary award and the ELSO early career award.

 

FIONA WATT UK

King's College, London

Stem cell-niche interactions in mammalian epidermis

Stem cell behaviour is controlled both by intrinsic mechanisms and by external signals from the local microenvironment or niche. Interactions with the niche are reciprocal, since stem cells are capable of remodelling their environment. Using adult epidermis as an experimental model, my lab is investigating the interplay between specific intrinsic and extrinsic signals in regulating stem cell fate. Using a range of in vitro and in vivo approaches, we have been able to define both soluble factors and extracellular matrix components in the niche and found that different fibroblast subpopulations communicate with the epidermis in different ways.

Biography

Fiona Watt is internationally recognised for elucidating the mechanisms that control epidermal stem cell renewal, differentiation and tissue assembly, and discovering how those processes are deregulated in disease. She obtained her DPhil from Oxford University and was a postdoc at MIT. She established her first laboratory at the Kennedy Institute in London and then moved to the Cancer Research UK (CR-UK) London Research Institute (formerly known as the Imperial Cancer Research Fund), where she worked for 20 years. From 2007 to 2012 she was the inaugural Herchel Smith Professor of Molecular Genetics at the University of Cambridge, Deputy Director of the Wellcome Trust Centre for Stem Cell Research and Deputy Director of the CR-UK Cambridge Research Institute. She has recently been appointed director of the Centre for Stem Cells and Regenerative Medicine at King's College London. Fiona Watt is a member of EMBO, a fellow of the Academy of Medical Sciences and the Royal Society and an Honorary Foreign Member of the American Academy of Arts and Sciences.

 

M. AZIM SURANI UK

The Gurdon Institute, University of Cambridge

Human Germline: Specification and Epigenetic Programming

Specification of primordial germ cells (PGCs) in human embryos probably occurs during the second week of gestation in early postimplantation embryos, which cannot be investigated in vivo.  To determine likely mechanism of primordial germ cell specification (PGCs), we have recently developed approaches for their specification from human pluripotent stem cells (hESCs) and induced pluripotent stem cells (iPSC)1. These in vitro derived PGCs showed conserved characteristics with authentic hPGCs isolated from later Wk5-Wk7 human embryos.  This unexpectedly revealed SOX17 as being necessary and sufficient for human germ cell fate, which is not the case for the mouse germline. The role of SOX17 is however dependant on the downstream expression of BLIMP1, which suppresses endodermal and mesodermal fates during the initiation of human PGC fate.  These genes also contribute to epigenome resetting in the early human germ cell lineage, which is critical for the transmission of genetic and epigenetic information to subsequent generations2.  Differences in mechanisms of PGC specification between mouse and human are likely to be due to the evolutionary divergence in their postimplantation development, as well as the mechanisms that confer competence for germ cell fate in pluripotent cells.  These studies will help to advance knowledge of human germ cell tumours, infertility and other diseases, as well as on the importance and consequences of transgenerational transmission of genetic and epigenetic information.   

1Irie, N et al., Cell 160, 253-268 (2015)
¬ 2 Tang, WWC, et al., Cell (in press, to be published on 4 June 2015) 
Supported by the Wellcome Trust, BIRAX, HFSP, BBSRC, MRC and CRUK.

Biography

Azim Surani was born in Kenya, and obtained his PhD in 1975 at Cambridge University under Professor Sir Robert Edwards FRS (Nobel Laureate, 2010). He discovered the phenomenon of Genomic Imprinting in 1984, and went onto identify several novel imprinted genes and their functions, and contributed to the mechanism of imprinting involving the erasure and re-establishment of DNA methylation. He was appointed the Marshall-Walton Professor at the Wellcome Trust Cancer Research UK Gurdon Institute in 1992, where he is currently Director of Germline and Epigenomics Research. His recent work has focused on the genetic basis for mammalian germ cell specification, and the initiation of the unique epigenetic program towards generating the totipotent state. He is a Fellow of the Royal Society and multiple awards, including a Royal Medal and the ISSCR McEwen Award for Innovation.