Bruce Lab

Laboratory of developmental biology and genetics (A. W. Bruce)

LAB SUMMARY

Research under my supervision in the 'Laboratory of Developmental Biology and Genetics (LDB&G)' is focussed on understanding the molecular mechanisms that underpin the preimplantation stages of mammalian embryo development, using the mouse embryo as our model system. Specifically, we address when and how do cells of the developing embryo first begin to differ from each other and how does this impact on the derivation of the three cell lineages present at the time of implantation at the late blastocyst stage? We are also interested in learning more about the molecular mechanisms that control the process of forming a fertilisable egg during the high asymmetric cell divisions of oocyte maturation, again using the mouse model. To address these questions we employ both 'classical' embryological techniques and 'cutting edge' molecular biology based approaches combined with computational integration of large genomic data sets. We also collaborate with our colleagues to provide 'genomics' based tools for the study of insect model organisms.

 

Please scroll down for more in depth information on our lab's research and our lab news segment (links to publications and lab staff are also provided at the bottom of this page)

*** Speculative Ph.D. & M.Sc. studentship applications welcomed ***

ENQUIRE ABOUT BOTH MASTERS AND PhD RESEARCH STUDENTSHIPS HERE

 

LINKS TO MY TEACHING MATERIALS; KMB758 (MOLECULAR BIOLOGY & GENETICS I) AND KMB358 (INTRODUCTION TO GENOMICS)

 

Take a moment to check out the FaceBook page of the Faculty of Science, University of South Bohemia

Also, please visit the webpages of RNDr Alena Krejčí Ph.D. relating to Notch signalling in Drosophila melanogaster.

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Dec' 16: Huge congratulations to Vasanth Thamodaran Ph.D. for successfully defending his Ph.D. thesis. We are all very proud of you and all that yoi have achieved and contributed to the group over the years. Best of luck in your future research, hopefully at the University of Osaka, Japan (we all hope the fellowhip comes good for you).

 

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Sep' & Oct' 16: A very big welcome to Michalea Kubickova & Stefanie Pezlj who join our lab to conduct Matsers and Bachelors level research projects. Good luck and may the force be with you!

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Sep' 16: Alexander Bruce presented a 'selected abstract' talk at the recent British Society for Developmental Biology Meeting in Edinburgh (UK) relating to our lab's recent publication in Open Biology (Vasanth Thamodaran as first author) on the role of p38-Mapk14/11 and primitive endoderm formation.

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Aug' 16: Congratulations to Lenka Veselovska for her successful application for a Marie Curie European Inter-European Fellowship. We're happy you'll be around for 2 years.

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Aug' 16: Congratulations to Vasanth Thamodaran for the publicationof his paper entitled "p38 (Mapk14/11) occupies a regulatory node governing entry into primitive endoderm differentiation during preimplantation mouse embryo development" in the journal Open Biology.

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Jun' 16: Congratulations to Sarah Schnabellehner for successfully defending her Bachelors project thesis this month; with the grade '1' excellent! Good luck in your forthcoming Masters degree at Uppsala in Sweden!

 

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Mar/Apr '16: Congratulations to Aleksandar Mihajlovic on the publicationof his paper entitled "Appropriate subcellular localisation of Angiomotin and assocaited Hippo-signalling activity, is regulated by active Rho-associated protein kinase, during preimplantation mouse embryo development" in Reproductive Biomedicine Online. Update Sept '16: Welldone for making the cover image of the printed journal too, good job!

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Oct '15: Welcome to our new undergraduate student, Michael Holzer. He joins our reserach group from the Joint Biological Chemistry programme with Johannes Kepler University in Linz. Good luck and may the force be with you!


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Aug '15: LDB&G Accepted Manuscript. Congratulations to Aleksandar Mihajlovic & Vasanth Thamodaran for having their manuscript entitled "The first two cell-fate decisions of preimplantation mouse embryo development are not functionally independent" accepted for publication in the journal Scientific Reports (lF: 5.578). Download PDF here

 

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Jul '15: The 2015 Confocal Microscopy and Image Analysis Workshop. A collabration between South Bohemia University (Faculty of Science, Department of Molecular Biology; Dr. Alexander Bruce and Dr. David Dolezel), Czech Academy of Sciences, Olympus (Czech Rep), Biplane/ Imaris and Gurdon Institute (University of Cambridge - Alex Sossick). A really useful week long event with over 30 participants (mostly post-graduate students in the early stages of their Ph.D research projects) learning microscopy from the fundamentals to the cutting edge. Well done everyone! Same again in 2017!

 

Photos here on AWB facebook page

 

To view the lab news archive scroll to the bottom of this page

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OUR LAB'S RESEARCH


1. OOCYTE-BASED RESESEARCH

The process of forming a functional mammalian oocyte within the ovary (Oogenesis) capable of supporting embryonic growth post-fertilisation can be summarised by the following scheme and accompanying figure:

1. Diploid Oogonium —(Oocytogenesis)-->

2. Diploid Primary Oocyte —(Meiosis I of Ootidogenesis)-->

3. Haploid Secondary Oocyte + First Polar Body  —(Meiosis II of Ootidogenesis)-->

4. Haploid Ootid + Second Polar Body, immediately after Sperm Fertilisation  —(Additional Ovum Maturation)-->

5. Diploid Zygote, and subsequent preimplantation stage embryonic development.

n.b. terms given in parentheses describe the name given to that particular stage of oogenesis


In female humans and mice the process of oocytogenesis is completed around the time of birth and the prevailing dogma dictates that no further primary oocytes are generated thereafter (in stark contrast tocontinuous spermatogenesis in males). The process of forming ootids (ootidogenesis) occurs during two rounds of meiosis and is initiated prenatally. However, ootidogenesis is stalled in the prophase stage of meiosis I so that by the time of birth the development of all the primary oocytes within the ovary is halted at this stage. Under the influence of the menstrual cycle hormones (follicle stimulating hormone and luteinizinghormone), meiosis I resumes in a sub-population of primary oocytes (and there is a time window in which sister chromosomes can recombine leading to genetic cross over). Ovulation then takes place and the haploid secondary oocyte plus the first polar body is generated at which time meiosis II of ootidogenesis is initiated but is then arrested at the metaphase II stage. Upon sperm fertilisation, the secondary oocyte resumes meiosis II and extrudes the second polar body, thus forming the short-lived ootid, that then undergoes further maturation steps as a fertilised ovum, eventually forming a diploid zygote capable of further embryonic development.

In our lab, we are interested learning more about the molecular processes occurring when diploid primary oocytes are recruited into ootidogenesis and the mature into haploid secondary oocytes capable of being fertilised and supporting the preimplantation stages of embryonic development. We are particularly interested in the mechanisms that ensure the faithful segregation of chromosomes between the maturing oocyte and the extruded polar bodies (during meiosis I and II) and are functionally characterising a number of candidate target genes (using classical mouse genetics and RNAi/ mRNA microinjection and high resolution time-lapse microscopy techniques on oocytes maturing in culture). Moreover, we are also interested to learn more about how appropriate sperm-oocyte interactions are regulated to ensure only one sperm successfully penetrates and fertilised the egg (in particular regulation and functioning of the cortical granule reaction - see accompanying confocal micrograph of a projected oocyte stained for cortical granules).

2. PREIMPLANTATION EMBRYO DEVELOPMENT RESEARCH

Following oocyte fertilization, the mammalian zygote undergoes a series of prolonged cell cycle divisions that results in the generation of the mature blastocyst consisting of three distinct cell types. The outside surface of the embryo comprises an epithelium of differentiated cells called the trophectoderm (TE – that subsequently develop to form the embryonic component of the placenta), whilst a second population of differentiated cells, the primitive endoderm (PE – that primarily give rise to cells of the yolk sac), is found inside the embryo in contact with a fluid filled cavity and is distinct from other inner cells, the epiblast (EPI – that are the pluripotent progenitors cells of the foetus proper), that are completely buried inside the blastocyst structure. The differentiated TE and PE cells eventually develop after implantation to support and direct development of the foetus that is itself derived from the EPI population of cells. However, the early mammalian embryo can exhibit extraordinary regulative behaviour and can successfully develop even when cells or added or removed. Despite this developmental flexibility, evidence is emerging that early inter-cell asymmetries are able to bias individual cell-fate in semi-predictable ways suggestive of at least some early patterning in the mammalian embryo.

Consequently, our primary research objectives are to uncover novel molecular mechanisms that impact upon successful blastocyst formation under both unperturbed and regulative conditions. Furthermore, to better understand how the blastocyst’s three constituent lineages are derived from a single totipotent zygote during the considerable spatio-temporal constraints of pre-implantation development and to probe the functional importance of very early inter-cell asymmetries.

We employ classical embryological and molecular biological techniques to probe the mechanisms of action of candidate cell fate influencing genes, identified in genomic scale expression screens of the mouse embryo and mouse ES cells. Hence, we anticipate that our multi-disciplined approach, investigating the ‘in vivo’ balance between cell differentiation and retention of pluripotency in early mouse embryogenesis, will not only advance our fundamental knowledge of one of the most enigmatic periods of development but will also provide insight to clinical/ veterinary embryologists and those clinicians working in the field of regenerative stem cell-based medicine.


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WHERE ARE WE? (click to see Google Maps)

Laboratory of Developmental Biology

and Genomics

Department of Molecular Biology

Faculty of Science (building B - see above)

University of South Bohemia

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THANKS TO OUR RESEARCH FUNDERS

 

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LABORATORY NEWS ARCHIVE


 

May '15:
Welcome to Lenka Veselovska who joins the lab to start her first post doc (on a University of South Bohemia funded bridging fellowship), after successfully defending her thesis at the University of Cambridge (Babraham Institute) earlier this month. Well done and welcome. We're not quite Slovakia, but close enough we hope! We all wish you all the best with your research.

 

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Aug. '14: Science should never come to this, STAP cell controversy or not! Stem-cell scientists mourn loss of brain engineer. RIP Yoshiki Sasai

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Jul. '14: We made it! The LDB&G finally moves to its new home . . . 10 metres from our old one!

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Jun. '14: Congratulations to Marie Jakesova for passing the defence of her Bachelors dissertation/ research project today, with a grade 1 (excellent)! All the best from the rest of the lab.

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Apr '14: Welcome to Giorgio Virnicchi who joins the lab to start his Ph.D. Giorgio come to us from sunny Naples. We hope you will not find the Czech winters here in Ceske Budejovice too cold! Good luck with your research project from all of the lab.

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TOO GOOD TO BE TRUE !? (STAP Cell doubts)


Jan '14: CHECK IT OUT!  Researchers in Japan report on the derivation of hyper-pluripotent stems cells (termed STAP cells) from terminally differentiated post-natal tissue cells via simple transient and sublethal environmental stresses (such as low pH). THIS IS A GAME CHANGER! - read more at the Nature website!

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Jan '14: The Department of Molecular Biology Scientific Image Competition 2013 entrants can be viewed here (you can also view the entrants from 2012 and 2011). Many thanks to all the participants and for the high quality of images submitted.
1st Prize - Eva Horakova (Lukes lab)
2nd Prize - Aleksandar Mahajlovic (Bruce lab)
3rd Prize - Raquel Perez-Gomez (Krejci lab)

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Jan. '14: Aleksandar Mihajlovic of the Bruce lab wins second prize (in his own right this time!) in the 2013 Department of Molecular Biology's Image Competition with his image of two opposed mouse blastocysts. Congratulations to him from the rest of the lab!


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Nov '13: R.I.P. Dr. Fred Sanger, twice Nobel laureate and the 'Father of Genomics'. Without Fred's ground breaking work on protein and particularly DNA sequencing our world would be a comparatively impoverished place. We all owe a great deal to the fruits of his genius.


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Nov '13: The LDB&G has established confocal time-lapse microscopy in the laboratory. The movie shows a projected image of an 8- to 16-cell transition transgenic embryo expressing a Histone H2B-GFP reporter (magenta) with a frame interval of 20 minutes. Note the two asymmetric cell divsions (generating both outer and inner daughter cells) followed by a symmetric division (yielding two daughter cells on the outside of the embryo).

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Oct. '13: A very warm welcome to the lab for Sarah Schnabellehner. Sarah is a bachelors student from the joint Ceske Budejovice - Linz, Biological Chemistry programme who will be undertaking a research based project in the lab. Good luck Sarah!


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Sep. '13: Alexander Bruce gave a conference talk at the recent "Vita Nova International Education Event" held in Bratislava, Solvakia (20th -September 2013). The meeting was organised by MUDr. Peter Harbulák, PhD. (Centre for Gynaecology and Assisted Reproduction, Bratislava) and colleagues, to bring together scientific researchers and clinicians with common interests in the field of gynaecology and assisted reproduction, on the European level. The 2013 meeting focussed on assesing embryo quality and approaches to ovarian stimulation. Alex's talk was in the first session and was entitled "Generating different genetic expression patterns in the early embryo; insights from the mouse model." - see full conference programme here

 

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Aug. '13: Inaugral Lab Retreat of the 'Czech Oocyte and Embryo Club' in Valtice, South Moravia. A great event, with thanks to Martin Anger's lab for organisation. Next year South Bohemia . . . .

 

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May. 13': Online proof of Alexander Bruce's manuscript entitled 'Generating different genetic expression patterrns in the early embryo: insights from the mouse model (PubMed ID: 23768616)

 

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May. '13: A succesful lab social at the raising of the 'Majka' (aka Maypole) in the village of Rimov in South Bohemia. A good time had by all!

Thanks to Ender for the fancy photography!

 

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Mar. '13: A very big welcome to Ender Yalcinkaya who joins our group, from a clinical embryology background. Ender's arrival takes our 'nationality count' up to 6! Good luck with your experiments from the rest of the lab. We hope you find life in Budweis as exciting as in Istanbul!

 

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Jan. '13: Congratulations to Joan Alornyo for passing the defence of her Bachelors dissertation/ research project today, with a grade 1 (excellent)! All the best from the rest of the lab.

 

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Jan. '13: Alexander Bruce's lab has been awarded a 4 year project grant from the Grant Agency of the Czech Republic. - see here for the full list of GACR awarded project grants 2012; Medical and Biological Sciences panel

 

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Jan. '13: Aleksandar Mihajlovic of the Bruce lab wins joint second prize in the 2012 Department of Molecular Biology's Image Competition with his image of a mouse morula. Congratulations to him from the rest of the lab!

2012 Department of Molecular Biology's Image Entrants Gallery

 

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Dec. '12: Alexander Bruce gave a conference talk as the recent "Futures in Reproduction Conference" held at the University of Cambridge UK (14th - 16th December 2012). The meeting was organised as a celebration of the award of the 2010 Nobel Prize for Physiology or Medicine to Professor Sir Robert G. Edwards for his pioneering work in developing human in vitro fertilization (IVF). Alex's talk was entitled "Generating different genetic expression patterns in the early embryo; insights from the mouse model." - see full conference programme here

 

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Nov. '12: Alexander Bruce has been appointed to the editorial board of the scientific journal  'Reproductive Biomedicine Online (RBMoL)'. To run from Jan. '13 to Dec. '16

 

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Sep. '12: A very big 'official' welcome to our two new (2012) Ph.D. students. It's great to have Aleksandar Mihajlovic and Rajiv Rana as part of our team. We all wish you both (rapid) success in your research.

P.S. An additional welcome to our new undergraduate student Marie Jakesova. Good luck with your project!

 

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Aug. '12: Congratulations to memebers of the Bruce lab (plus the wider department) for helping to organise the 'First' Confocal Microscopy and Image Analysis Workshop" (9th August - 16th Augus 2012). Additional thanks to our official partners; Dr. Alex Sossick (The Gurdon Institute, Univserity of Cambridge), Olympus Czech Republic (Microscopy), BitPlane (Munich, Germany - Imaris), The Biology Centre of the Czech Academy of Sciences and The Faculty of Science University of South Bohmeia. Special thanks to the EU and Czech Governemnt for funding this inaugral event. The feedback was excellent and it is planned to make the workshop an biannual event to help train newly appointed Ph.D. students.

 

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Jan. '12: Vasanth Thamodaran of the Bruce lab wins the 2011 Department of Molecular Biology's Image Competition with his image of a mouse morula. Congratulations to him from the rest of the lab!

- 2011 Department of Molecular Biology's Image Entrants Gallery


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