WIMM PI
Curriculum Vitae
Personal Data
Name
Nationality
Email
Tatjana Sauka-Spengler
France
tatjana.sauka-spengler@imm.ox.ac.uk
Present Position
2014-present
Associate Professor of Genome Biology, MRC Senior Research Fellow,
WIMM, Radcliffe Department of Medicine, University of Oxford
2011-present
Group Leader, MRC Senior Research Fellow, WIMM, University of Oxford
2011-present
Visiting Associate, California Institute of Technology, Pasadena
Previous Positions
2008-2011
2003-2008
1999-2002
1996-1999
1993-1996
1992-1993
Senior Research Fellow, California Institute of Technology, Pasadena
Postdoctoral fellow, California Institute of Technology, Pasadena
Graduate student, Unit of Evolution and Development, University of Paris
Graduate student, Unit of Solid State Physics, University of Paris
Production co-ordinator - Film "Underground" CIBY 2000, Paris, France
Physics Teacher in the High School of Pardubice, Czech Republic
1
Research Achievements
My interdisciplinary training in physical and biological sciences has given me a strong
foundation in quantitative biology and an avid interest in resolving complex networks
underlying biological processes. During my postdoctoral work at the California Institute of
Technology, I defined and characterized the gene regulatory network (GRN) that underlies
neural crest (NC) formation in a basal extant vertebrate, the sea lamprey. These studies led
to the pivotal discovery that the modular organization and interactions within NC GRN at
early developmental steps were highly conserved to the base of vertebrates. During this
work, I pioneered a number of genomic, embryological, knockdown and transgenic
techniques that helped launch lamprey into a new developmental and molecular model
system, and I was also involved at the forefront of the genome project. Subsequently, I
developed elegant methods for rapid identification and dissection of NC enhancers and
further refinement of the NC GRN in other vertebrates. In my new lab at the Weatherall
Institute of Molecular Medicine, my laboratory has continued these studies to perfect new
technologies for systems-level regulatory profiling of small embryonic cell populations, using
chick and zebrafish models. Those include cell-specific in vivo biotinylation of target
regulators and cellular compartments, microChIP-seq and nascent RNA-seq protocols,
enhancer-driven knockdown and enhanceosome pulldown constructs, as well as multiplex
transcriptional and enhancer analysis using NanoString nCounter and multicolour enhancer
assays that can be applied to individual embryos. The unique biochemical and profiling
toolkit we have developed enables us to study biological circuits in vertebrate embryos in a
fashion that was previously only possible in cell lines.
What are the Future Aims of Your Current Group?
Our central interest is to elucidate the gene regulatory programme controlling cellular identity
and function of neural crest (NC) cells. The NC is a multipotent embryonic cell population
that contributes derivatives to a wide variety of structures including sensory and autonomic
ganglia, the craniofacial skeleton, and pigmentation of the skin. We focus on premigratory NC
as this stage is intimately linked to maintenance of NC multipotency and the onset of the
epithelial to mesenchymal transition (EMT). To elucidate the underlying regulatory circuitry,
we are using a non-biased, systems-level approach that consists of epigenomic and
transcriptional profiling of specific NC populations isolated from intact embryos. We
systematically analyse chromatin architecture of developing NC cells, map chromatin and
transcriptional signatures and computationally correlate these datasets to identify/classify
active regulatory sites. For the next five years, our main aims are to probe hierarchical
relationships within the GRN by (1) testing functional activity of identified cis-regulatory
regions, (2) analysing enhancers computationally and experimentally to identify
corresponding transcription factor-controlled regulatory subcircuits, (3) testing hierarchical
connections within subcircuits by analysing direct binding of upstream factors and expression
of downstream targets after their perturbation. All these components then will be linked into a
comprehensive representation of the premigratory NC GRN. In parallel, we are developing
novel approaches in zebrafish to study dynamic association and function of chromatin
remodellers with the NC active loci, as well as involvement of long non-coding RNAs in the
regulatory control of pre-migratory neural crest. NC GRN information will, in turn, be used to
establish new protocols for directed differentiation of stem cells into neural crest progenitors,
thereby recapitulating the endogenous developmental program of neural crest formation. We
will continue developing technology to probe networks in vivo, to understand how
perturbations therein may lead to neurocristopathies and birth defects in humans.
2
How do These Aims Contribute to the Understanding and/or Management of Human
Disease
During development, finely orchestrated regulatory programs control cell fate decisions,
differentiation and morphogenesis, ultimately leading to formation of the adult organism.
This raises an intriguing question: how are these programs, encoded at the genomic level,
translated into complex networks of interacting biological components (genes, proteins,
RNA)? The answer to this question is essential for understanding human diseases and birth
defects that result when these biological circuits go awry. For example, neural crest-related
anomalies, such as craniofacial and cardiac septal malformations, account for ~1/3 of
congenital birth defects. Furthermore, dysregulated neural crest derivatives give rise to a
number of pediatric and adult tumours such as neuroblastomas and melanomas. In addition,
there is broad interest in using the regenerative capacity of the neural crest (NC) in stem cellbased treatments, due to their unique multipotency and developmental plasticity. Our long
term aim is to use core gene regulatory network (GRN) information to understand
mechanisms leading to birth defects, and to develop new approaches to derive NC
progenitors from stem cells for therapeutic purposes.
We have also developed novel technology for GRN analysis of specific embryonic cell
populations in vivo using zebrafish, that is very useful for studying disease mechanisms.. In
recent years, zebrafish has become an important system for understanding human disease.
Zebrafish have the same genes, cell types, tissues, organs and biological circuits as
humans, ensuring that the lessons from this model can be directly applied to human health.
Our tools enable genetically encoded protein tagging and genome-wide micro-profiling,
making possible gene regulatory analysis in specific zebrafish cell populations. Thus, we are
uniquely poised to address mechanistic aspects of not only altered developmental processes
but also those activated during inflammatory response, in diseased states or during organ
regeneration. As a consequence, we are engaging in numerous collaborations with other
groups within the Institute taking advantage of our approaches.
Lay Summary of Research
A major challenge in biology today is to understand the processes that control formation of
complex organisms. During development, a single cell, the fertilized egg, is transformed into
a mature adult comprised of millions of cells, and dozens of organs, each with unique identity
and function. In recent years, it has become clear that gene circuits, somewhat analogous to
electrical circuits, are critical for the sequential processes that transform embryos into the
adult form. Decoding and mapping these gene regulatory circuits at a “systems” level will
help understand not only normal processes, but also how mistakes or disruptions during
disease can cause these circuits to go awry, leading to birth defects and cancers.
Understanding these circuits can lead to treatments. Our aim is to decipher the gene
regulatory circuitry responsible for formation of an important embryonic cell type called the
“neural crest.” This cell population, specific to vertebrate embryos, is a type of stem cell, that
can give rise to a number of different cell types and tissues. These include parts of the
nervous system, major blood vessels and heart valves, bones of the face, and pigmentation
of the body. Neural crest defects are responsible for ~1/3 of all congenital birth defects,
including cleft palate, other facial abnormalities and a number of syndromes including
DiGeorge’s sydrome, with defects in the heart, thymus and thyroid glands, and Hirschsprung
disease with defects in gastrointestinal tract movements. Due to their highly migratory
nature, neural crest cells spread much like cancer cells and indeed are the root of cancers
such as melanoma. Thus understanding neural crest regulation has the potential to provide a
better understanding of not only normal development but also numerous human
malformations and diseases. In addition, there is broad interest in using their regenerative
capacity in stem cell-based treatments.
3
All Publications Over the Past 5 Years
(h-index 23, Citations 2208)
Bassett AR, Azzam G, Wheatley L, Tibbit C, Rajakumar T, McGowan S, Stanger N, Ewels
PA, Taylor S, Ponting CP, Liu JL, Sauka-Spengler T, Fulga TA (2014). Understanding
functional miRNA-target interactions in vivo by site-specific genome engineering. Nat
Commun. Aug 19;5:4640.
Parker HJ, Sauka-Spengler T, Bronner M, Elgar G (2014). A reporter assay in lamprey
embryos reveals both functional conservation and elaboration of vertebrate enhancers.
PLoS One. Jan 9;9(1):e85492.
Modrell MS, Hockman D, Uy B, Buckley D, Sauka-Spengler T, Bronner ME, Baker CV
(2014). A fate-map for cranial sensory ganglia in the sea lamprey. Dev Biol. Jan
15;385(2):405-16.
Betancur P, Simões-Costa M, Sauka-Spengler T, Bronner ME (2014). Expression and
function of transcription factor cMyb during cranial neural crest development. Mech Dev.
132:38-43.
Simões-Costa M, Tan-Cabugao J, Antoshechkin I, Sauka-Spengler T, Bronner ME (2014).
Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory
network. Genome Res. 24(2):281-90.
Simoes-Costa M, Tan-Cabugao J, Antoshechkin I, Sauka-Spengler T and Bronner ME
(2013). Migratome analysis reveals novel players in the cranial neural crest gene
regulatory network (Genome Research In Press).
Amemiya, C.T. et al. (2013) The African coelacanth genome provides insights into tetrapod
evolution. Nature 496, 311–316.
Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang Net et al. (2013). Sequencing of the
sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution.
Nat Genet. Apr;45(4):415-21, 421e1-2.
Simoes Costa M, McKeown SJ, Sauka-Spengler T* and Bronner ME* (2012). Dynamic and
differential regulation of FoxD3 neural crest expression is encrypted in the genome. *equal
senior and corresponding authors PLoS Genet. Dec;8(12):e1003142.
Hu N, Strobl-Mazzulla P, Sauka-Spengler T, Bronner ME (2012). DNA methyltransferase3A
as a molecular switch mediating the neural tube-to-neural crest fate transition. Genes
Dev. 26(21):2380-5.
Uy BR, Simoes-Costa M, Sauka-Spengler T, Bronner ME (2012). Expression of Sox family
genes in early lamprey development. Int J Dev Biol. 56(5):377-83.
Prasad MS, Sauka-Spengler T, LaBonne C. (2012) Induction of the neural crest state:
control of stem cell attributes by gene regulatory, post-transcriptional and epigenetic
interactions. Dev Biol. 366(1):10-21.
Parker HJ, Piccinelli P, Sauka-Spengler T, Bronner M, Elgar G. (2011) Ancient Pbx-Hox
signatures define hundreds of vertebrate developmental enhancers. BMC
Genomics.12(637).
Häming D, Simoes-Costa M, Uy B, Valencia J, Sauka-Spengler T, Bronner-Fraser M. (2011)
Expression of sympathetic nervous system genes in Lamprey suggests their recruitment
for specification of a new vertebrate feature. PLoS One. 6(10):e26543.
Betancur P, Sauka-Spengler T, Bronner M. (2011) A Sox10 enhancer element common to
the otic placode and neural crest is activated by tissue-specific paralogs. Development.
138(17):3689-98.
Sauka-Spengler T, Bronner M. (2010) Snapshot: neural crest. Cell. 143(3):486-486.e1.
Cerny R, Cattell M, Sauka-Spengler T, Bronner-Fraser M, Yu F, Medeiros DM.(2010)
Evidence for the prepattern/cooption model of vertebrate jaw evolution. Proc Natl Acad
Sci U S A. 107(40):17262-7.
Strobl-Mazzulla PH, Sauka-Spengler T and Bronner-Fraser M. (2010) Histone Demethylase
4
JmjD2A Regulates Neural Crest Specification. Dev Cell. 19(3):460-8.
Betancur P, Bronner-Fraser M and Sauka-Spengler T (2010) Genomic code for Sox10
activation reveals a key regulatory enhancer for cranial neural crest. Proc Natl Acad Sci U
S A. 107(8):3570-5.
Betancur P, Bronner-Fraser M, Sauka-Spengler T (2010). Assembling neural crest
regulatory circuits into a gene regulatory network. Annu Rev Cell Dev Biol. 26:581-603.
Smith JJ, Stuart AB, Sauka-Spengler T, Clifton SW and Amemiya CT (2010) Development
and analysis of a germline BAC resource for the sea lamprey, a vertebrate that undergoes
substantial chromatin diminution. Chromosoma. 119(4):381-9.
Nikitina N, Bronner-Fraser M and Sauka-Spengler T (2008) Emerging Model Organisms: the
Sea Lamprey Petromyzon marinus. Cold Spring Harbor Laboratory Press 1:402-412.
Nikitina N*, Sauka-Spengler T* and Bronner-Fraser M (2008) Dissecting Early Regulatory
Relationships in the Lamprey Neural Crest Gene Regulatory Network. *Both authors
contributed equally. Proc Natl Acad Sci U S A. 105(51):20083-8.
Sauka-Spengler T and Bronner-Fraser M. (2008) Evolution of the neural crest viewed from a
gene regulatory perspective. Genesis. 46(11):673-82.
Sauka-Spengler T and Bronner-Fraser M. (2008) Insights from a sea lamprey into the
evolution of neural crest gene regulatory network. Biol Bull. 214(3):303-14.
Putnam NH et al. (2008) The amphioxus genome and the evolution of the chordate
karyotype. Nature. 453(7198):1064-71.
Sauka-Spengler T and Bronner-Fraser M. (2008) A gene regulatory network orchestrates
neural crest formation. Nat Rev Mol Cell Biol. 2008 9(7):557-68.
Sauka-Spengler T and Barembaum M. (2008) Gain and loss of function approaches in the
chick embryo. Methods Cell Biol. 87:237-56.
Sauka-Spengler T, Meulemans D, Jones M, Bronner-Fraser, M. (2007) Ancient evolutionary
origin of the neural crest gene regulatory network. Dev Cell. 13:405-20.
Ten Key Publications Throughout your Career
Simões-Costa M, Tan-Cabugao J, Antoshechkin I, Sauka-Spengler T, Bronner ME. (2014).
Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory
network. Genome Res. 24(2):281-90.
Smith JJ, Kuraku S, Holt C, Sauka-Spengler T, Jiang Net et al. (2013). Sequencing of the
sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution.
Nat Genet. Apr;45(4):415-21, 421e1-2.
Simoes Costa M, McKeown SJ, Sauka-Spengler T* and Bronner ME* (2012). Dynamic and
differential regulation of FoxD3 neural crest expression is encrypted in the genome. *equal
senior and corresponding authors PLoS Genet. Dec;8(12):e1003142.
Hu N, Strobl-Mazzulla P, Sauka-Spengler T, Bronner ME (2012). DNA methyltransferase3A
as a molecular switch mediating the neural tube-to-neural crest fate transition. Genes
Dev. 26(21):2380-5.
Strobl-Mazzulla PH, Sauka-Spengler T and Bronner-Fraser M. (2010) Histone Demethylase
JmjD2A Regulates Neural Crest Specification. Dev Cell. 19(3):460-8.
Betancur P, Bronner-Fraser M and Sauka-Spengler T (2010) Genomic code for Sox10
activation reveals a key regulatory enhancer for cranial neural crest. Proc Natl Acad Sci U
S A. 107(8):3570-5.
Betancur P, Bronner-Fraser M, Sauka-Spengler T (2010). Assembling neural crest
regulatory circuits into a gene regulatory network. Annu Rev Cell Dev Biol. 26:581-603.
Nikitina N*, Sauka-Spengler T* and Bronner-Fraser M (2008) Dissecting Early Regulatory
Relationships in the Lamprey Neural Crest Gene Regulatory Network. *Both authors
contributed equally. Proc Natl Acad Sci U S A. 105(51):20083-8.
5
Sauka-Spengler T and Bronner-Fraser M. (2008) A gene regulatory network orchestrates
neural crest formation. Nat Rev Mol Cell Biol. 2008 9(7):557-68.
Sauka-Spengler T, Meulemans D, Jones M, Bronner-Fraser, M. (2007) Ancient evolutionary
origin of the neural crest gene regulatory network. Dev Cell. 13
Markers of Esteem
2013
Lister Institute Research Prize
2013
March of Dimes Basil O’Connor Research Award
2011
MRC Senior Research Fellowship
2009
ARRA award (American Recovery and Reinvestment Act)
2006
CIRM Stem Cell Post Doctoral Fellowship
Current Grant Support
MRC Senior Research Fellowship, 2011-2016
Institutional Strategic Support Fund (Wellcome Trust), 2014
Ovarian Cancer Initiative, 2014
John Fell OUP Fund, 2014
Lister Institute Research Prize 2013
Basil O’Connor Research Award, March of Dimes, 2013
BHF CRE Research Excellence 95, 2012-2014
Oxford Cancer Research Centre, 2013-2014
Sponsor of Wellcome Trust Studentship (with V. Cerundolo), 2011-2015
Sponsor of Swiss National Foundation Fellowship, 2013-2014
Sponsor of Trinity College Junior Research Fellowship, 2013-2016
John Fell Funding for NanoString nCounter (with A. McMicheal)
Cephalosporin Funding for NanoString nCounter (with A. McMicheal)
John Fell Funding for Zebrafish Facility Expansion (with R. Patient)
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£1,100,688
£45,000
£200,000
£15,000
£200,000
£97,000
£50,000
£15,000
£120,000
£32,000
£80,000
£50,000
£60,000
£100,000