Archive for the ‘knockout’ Category

A report on the 7th European Short Course on Laboratory Animal Science in Strasbourg, organized by Charles River

Friday, February 14th, 2014
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A report on the 7th European Short Course on Laboratory Animal Science in Strasbourg, organized by Charles River

A report on the 7th European Short Course on Laboratory Animal Science in Strasbourg, organized by Charles River

The 7th European Short Course on Laboratory Animal Science, organized by Charles River, just closed in Strasbourg, France, after three days of interesting presentations and discussions at the intersection between animal welfare, animal experimentation, current guidelines and legislation, biomedical research from academia and industry and society perception on these topics. The Organizers should be praised for the selection and variety of topics, as well as for the smooth and pleasant running of the entire course, which included an enjoyable visit to an old typical cellar from the Alsace region along with a wine-testing Gala dinner.

Several ISTT members participated in this event, including organizers (Cyril Desvignes, Jean Cozzi), members of the steering committee (Johannes Wilbertz), invited speakers (Belén Pintado, Yann Herault, Ignacio Anegon, Lluís Montoliu), and participants (Marcello Raspa, Ferenc Erdelyi, Gabor Szabo,…) among other.

During this course, the recent EU Directive 2010/63 on the protection of animals used in research and its implication on the use of animals in biomedical research and policies throughout Europe was discussed, from different angles, by Magda Chlebus, Gill Fleetwood, Thierry Decelle, Patri Vergara and Belén Pintado. Topics covered included the new training courses and competencies to work with experimentation animals in Europe, the animal-welfare bodies and the current understanding of the 3R’s paradigm. Javier Guillén compared, side by side, the new EU Directive with the current Guide in the US and highlighted their many coincidences, suggesting that a combined use of both documents would be ideal for the adoption of successful animal care and use programs. Jan-Bas Prins, current president of FELASA, presented his view of the field of laboratory animal sciences, before the implementation of this new EU Directive, as an opportunity and a positive challenge to interface and exchange knowledge with many other players involved.

Health monitoring programs, rodent microbiologic surveillance, methods employed to detect all these pathogens robustly in laboratory animal facilities and the updated recommendations from FELASA, recently published in Laboratory Animals, were presented by William Shek, Guy Mulder, Stéphanie Durand and Axel Kornerup Hansen. Operational and technical aspects of animal facilities were discussed by Alberto Gobbi and Peter Dockx, whereas the issues related with occupational health and safety program evaluations were presented by Jann Hau.

Examples of the use of rodent animal models in biomedical research, in academia, by James Di Santo and Andrea Bertotti, as well as in the industry, by Joyce L. Young, were discussed. The importance of genetic quality in mouse research as well as the complexity of mouse genome and the impact of the genetic background on phenotypes was presented by Charles Miller and Lluís Montoliu, respectively. The procedures conducted at the International Mouse Phenotyping Consortium (IMPC) as well as the challenges they encountered during the deployment of this impressively large enterprise were presented and discussed by Sara Wells and, by the local representative, Yann Herault, Director of the French Mouse Clinic, ICS, in Strasbourg, who delivered the closing talk.

The newest technologies in stem cell biology and animal transgenesis were also present at this 7th Short Course. Hongkui Deng summarized the most innovative approach he devised to prepare induced-pluripotent cells from somatic cells, using a cocktail of four chemicals, four molecules that mimicked the induction signals described by Shinya Yamanaka. The new logics for the production of targeted genetic modifications, using editing or engineered nucleases (Meganuclease, ZFNs, TALENs, CRISPRs) in mice and rats was presented by Ralf Kuehn and Ignacio Anegon, respectively.

The choice of rodent anaestesia protocols was discussed by Aurelie Thomas, whereas the various methods for euthanasia in rodents were presented by Huw Golledge. On the last day, Aurora Bronstad summarized the work done at the AALAS-FELASA joint working group on harm-benefit analysis, whereas Katrina Gore highlighted the need for more robust analytical procedures in research protocols involving animal experimentation, in order to optimize the rate of success of pre-clinical drugs.

In summary, the 7th Edition of this biennial Charles River Short Course on Laboratory Animal Science in Europe, attended by some 120 participants, was an excellent opportunity to update information related to animal welfare, EU legislation and transposition difficulties in various countries, newest technologies, mouse genomics and genetics, large mouse consortia and numerous important topics that are relevant for animal facility managers, researchers, veterinarians and anyone else interested in the best use of animals in experiments, according to current laws and recommendations.

More than 27,000 messages on animal transgenesis available to ISTT members through ISTT_list and tg-l archives

Sunday, February 9th, 2014
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More than 27,000 messages on animal transgenesis available through ISTT_list and tg-l archives

More than 27,000 messages on animal transgenesis available through ISTT_list and tg-l archives

One of the most important assets of the International Society for Transgenic Technologies (ISTT), is the amount of information on animal transgenesis accummulated through the archives of the ISTT_list and tg-l email lists. Currently, more than 27,000 messages are fully available to ISTT members, conveniently organized in searchable and dynamic archives. The traditional transgenic-list (tg-l), operative since 1996 and offered from the ISTT web server since the end of 2011, has distributed over 22,000 messages since then, whereas the ISTT_list, associated and born with our Society in 2006, has disseminated some 5,000 messages, discussing both lists on almost each and every topic, issue or situation related directly or indirectly with animal transgenesis. All this endless information resource is fully available to ISTT members, through powerful search engines. Non-ISTT members subscribing to tg-l have access only to the most recent messages distributed through the tg-l, using the simple search engine, which allows simple searches and outputs the 50 most recent messages discussed on the subject of interest. In contrast, ISTT members have access to more sophysticated searching engines and the output always contains all messages archived on the matter investigated.

Obtaining granted access to these rich sources of information is very easy and cheap. Simply apply for ISTT membership! Submit now your application to become a member of the ISTT and you will get immediate and full access to all these messages.

Updated scientific and workshop programmes for the TT2014 meeting in Edinburgh

Friday, January 10th, 2014
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Upades scientific and workshop programmes for TT2014 meeting in Edinburgh: Please, register today!.

Upades scientific and workshop programmes for TT2014 meeting in Edinburgh: Please, register today!.

The scientific and zebrafish transgenesis hands-on workshop programmes prepared for the 12th Transgenic Technology (TT2014) meeting, to be held in Edinburgh (Scotland, UK), on October 6-8 (workshop on October 8-10) 2014,  have been recently updated by the Organizers, chaired by Douglas Strathdee (Glasgow, UK). These rewarding updates further increased the already high quality and interest for this popular conference series, promoted from the International Society for Transgenic Technologies (ISTT), the most important forum where to discuss the state-of-art of animal transgenic technology, to share new developments, to review the deployment of the new methods that have recently being devised and, in summary, an excellent arena where to easily meet, face-to-face, the most relevant key-players in the field while providing a wonderful excuse to gather and ex-change experiences with the entire ISTT family of members.

The updated list of confirmed invited speakers attending the TT2014 meeting (6-8 October 2014) includes:

  • David Adams, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  • Ignacio Anegon, Center for Research in Transplantation and Immunology, Nantes, France
  • James Bussell, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  • Ian Chalmers, MRC Centre for Regenerative Medicine, The University of Edinburgh, UK
  • Stephen Ekker, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA
  • Anna-Katerina Hadjatonakis, Developmental Biology Program, Sloan-Kettering Institute, New York, USA
  • Peter Hohenstein, The Roslin Institute and Royal Dick School of Vetinary Studies & MRC IGMM, University of Edinburgh, UK
  • Rudolf Jaenisch, Whitehead Institute for Biomedical Research, Nine Cambridge Center Cambridge, USA
  • Jos Jonkers, Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Keith Joung, Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA
  • Alexandra Joyner, Developmental Biology Program, Sloan-Kettering Institute, New York, USA
  • Koichi Kawakami, Division of Molecular and Developmental Biology, National Institute of Genetics, Shizuoka, Japan
  • Michael McGrew, Division of Developmental Biology, The Roslin Institute and Royal Dick School of Veterinary Studies, University of Edinburgh, UK
  • Daniel J Murphy, Beatson Institute for Cancer Research, University of Glasgow, UK
  • James Murray, Department of Animal Science and Department of Population Health and Reproduction, University of California, Davis, California, USA
  • Stephen Murray, The Jackson Laboratory, Bar Harbor, Maine, USA
  • Lluis Montoliu, ISTT President, Organising Committee, National Center of Biotechnology (CNB), CSIC, Madrid, Spain
  • Vasilis Ntziachristos, Technische Universität Mu?nchen, Munich, Germany
  • Elizabeth Patton, MRC Human Genetics Unit & MRC IGMM, University of Edinburgh, UK
  • Pawel Pelczar, Institute of Laboratory Animal Science, Zürich, Switzerland
  • Jan-Bas Prins, Leiden University Medical Centre, The Netherlands
  • Janet Rossant, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada (ISTT Prize)
  • Angelika Schnieke, Livestock Biotechnology, WZW Center of Life Science, Freising-Weihenstephan, Germany
  • Kai Schönig, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany
  • William Skarnes, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
  • Austin Smith, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Francis Stewart, Biotechnology Center of the TU Dresden, Germany
  • Sara Wells, MRC Harwell, Oxfordshire, UK
  • Jacqueline White, Wellcome Trust Sanger Institute, Hinxton, Cambridge UK

The updated list of confirmed invited speakers & instructors attending the hands-on zebrafish transgenesis workshop taking place immediately after the TT2014 meeting (8-10 October 2014) includes:

  • Liz Patton, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh
  • Carl Tucker, Biomedical Research Resources, The University of Edinburgh
  • Tim Czopka, Centre for Neuroregeneration, The University of Edinburgh
  • Koichi Kawakami, Division of Molecular and Developmental Biology, National Institute of Genetics, Shizuoka, Japan
  • Stephen Ekker, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA
  • Keith Joung, Department of Pathology, Massachusetts General Hospital and Harvard Medical School
  • Henry Roehl, Department of Biomedical Science, The University of Sheffield
  • Robert Kelsh, Centre for Regenerative Medicine and Department of Biology and Biochemistry, The University of Bath
  • Martin Denvir, The University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh
  • David Lyons, Centre for Neuroregeneration, The University of Edinburgh
  • Dirk Seiger, Centre for Neuroregeneration, The University of Edinburgh
  • Karthikeyani Paranthaman, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh

Abstracts: All TT2014 participants are encouraged to submit their work as an abstract for poster presentation at the TT2014 meeting. Abstracts should be submitted no later than June 30, 2014. Accepted abstracts will be published in the scientific journal Transgenic Research (Springer), to which the ISTT is associated. A limited number of abstract submissions will be selected and invited to present their findings in the form of a short oral presentation within the main meeting program. Abstracts are invited on all aspects of Transgenic Technologies, including the conference themes as listed below:

  • New technologies in animal transgenesis
  • Embryo stem cells
  • Target nucleases or Editing nucleases (ZFNs, TALENs, CRISPRs)
  • Large-scale phenotyping
  • Animal Biotechnology
  • Imaging with transgenic animals
  • Mouse models of human disease
  • Zebrafish models of human disease and transgenesis
  • Animal ethics and welfare

Registration for both the TT2014 meeting and the zebrafish transgenesis workshop are OPEN. Registration for the TT2014 meetings starts at 265 UK Pounds for technician/student ISTT members and progressively increases for the rest of categories of delegates. ISTT members are always entitled to reduced registration fees. Registration for the zebrafish transgenesis workshop is independent, with an extra cost of 275 UK Pounds , and only open to delegates that have also registered to attend the TT2014 meeting. The early bird reduced registration fees are operative until July 31, 2014. Thereafter, registration will be progressively become more expensive. Hence,  please register by July 31, 2014 to benefit from reduced registration fees.

ISTT Registration Awards: Application to ISTT registration awards for the TT2014 meeting is OPEN. A minimum of six registration awards for ISTT members will be sponsored by the International Society for Transgenic Technologies (ISTT). Applications should be sent, along with the registration confirmation and the requested additional documents to istt@transtechsociety.org by June 30, 2014. The ISTT will pay the Registration Fee of all applicants selected for an award. Please note that applicants not selected for an award are required to pay the coresponding registration fee. Please note the Award covers registration fees and attendance at all social events, however, does not cover travel, accommodation expenses or attendance at pre meeting events. Award decisions will be communicated by July 15, 2014 and awardees will receive a diploma at the TT2014 Meeting. Deadline for submitting application for ISTT Registration Awards for TT2014: 30 June 2014. Registration Award decisions will be communicated by 15 July 2014.

Looking forward to meeting you all in Edinburgh!

 

Cell-permeable Cre recombinase for rapid conversion of EUCOMM/KOMP-CSD alleles

Wednesday, November 13th, 2013
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Rapid conversion of EUCOMM/KOMP-CSD alleles in mouse embryos using a cell-permeable Cre recombinase. (Figure 1 from Ryder, Doe et al. Transgenic Research, 2013 Nov 7. DOI: 10.1007/s11248-013-9764-x)

Rapid conversion of EUCOMM/KOMP-CSD alleles in mouse embryos using a cell-permeable Cre recombinase. (Figure 1 from Ryder, Doe et al. Transgenic Research, 2013 Nov 7. DOI: 10.1007/s11248-013-9764-x)

Our colleagues from the Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK, most of them ISTT members, have just published a very interesting paper in Transgenic Research, the scientific journal associated with the International Society for Transgenic Technologies (ISTT),  describing the use of a cell-permeable Cre recombinase for the rapid conversion of EUCOMM/KOMP-CSD alleles directly in mouse embryos, hence avoiding the traditional breeding of mice produced with the original tm1a alleles with Cre-transgenic mouse lines to produce non-conditional knockout alleles (tm1b allele). This innovative procedure saves time, money, and, most importantly, many animals, thus contributing to animal welfare.

Rapid conversion of EUCOMM/KOMP-CSD alleles in mouse embryos using a cell-permeable Cre recombinase.
Ryder E, Doe B, Gleeson D, Houghton R, Dalvi P, Grau E, Habib B, Miklejewska E, Newman S, Sethi D, Sinclair C, Vyas S, Wardle-Jones H; Sanger Mouse Genetics Project, Bottomley J, Bussell J, Galli A, Salisbury J, Ramirez-Solis R.
Transgenic Res. 2013 Nov 7

Workshop report: animals bred, but not used in experiments

Wednesday, October 23rd, 2013
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Workshop:  “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)

Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)

Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands.

Experiments in biomedical science use large numbers of laboratory animals. It is a fact that to provide these animals, regularly more animals are bred than are finally used in the experiments planned. The Ministry of Economic Affairs as the competent body of the Netherlands had asked Prof. Coenraad Hendriksen and Dr. Jan-Bas Prins to organize a workshop to identify the reasons for the breeding of surplus animals and to devise recommendations as to how the number of animals that are bred but not used can be reduced to a minimum.

A number of experts from different fields of laboratory animal science were invited for a two day workshop to the Hotel Duin & Kruidberg in Santpoort, a town close to Amsterdam, to discuss these issues and to develop a paper for the Dutch authorities. Obviously, many of the laboratory animals bred are genetically altered (GA) animals. Moreover, techniques to cryopreserve GA animal lines could be a means to reduce the number of animals that are bred. The invitation was therefore extended to the ISTT to send a representative to take part in this workshop.

Here, I will give a short summary of the topics that have been discussed and of the outcomes. However, I refer you to the final report of the workshop, parts of which have been developed within individual small workgroups and will be put together into a final document by the kind efforts of Coenraad and Jan-Bas. I will inform you immediately upon the publication of this report.

A topic central to the discussion was the identification of reasons for the production of animals that are then not used in experiments. A major reason for this is the production of unwanted sexes and unwanted genotypes. The participants agreed that good planning can considerably reduce the number of surplus animals. At the same time, resources can be saved and either used for additional experiments or for cost reduction. However, breeding schemes with multiple alleles, as well as the organization of a facility, can be complex. A strong need for counseling as well as education of users of laboratory animals was identified, to make them competent to plan accordingly. The centralization of the breeding colonies under the responsibility of the facility management was discussed as a possibility to streamline breeding strategies. On the other hand, for the time being, this does not seem to be feasible for very many facilities. Local Animal Welfare Committees should evaluate local SOPs and develop a catalogue of best practices to help keep surplus animals to a minimum. GA animal lines should be cryopreserved immediately after their creation when there is no need to breed extra animals for this purpose and when animals from test rederivations can be used for experiments or for the breeding colony. Thereby, the lines are protected from disaster and from genetic drift at the same time, live mice can be terminated at any time, and the lines can be easily shipped to collaborators. Lines should be made available to collaborators as early as possibly to avoid generating the same line at different places. In case expertise for cryopreservation is lacking, lines can be donated to repositories like EMMA where they are cryopreserved free of charge. Investigators should always consider sharing lines with the scientific community through such repositories.

A second important topic discussed during the workshop was the use of new technologies for the generation of GA animals as well as for their experimental analysis. New lines should be directly generated on the desired background. In case backcrossing is needed, speed congenic strategies should be used to reduce the number of animals needed during that process. Technologies utilizing the targeting of nucleases to the locus of interest (ZFNs, TALENs, CRISPER/Cas9) promise to eventually allow the generation of GA lines with reduced numbers of animals directly on the desired background. Complex strategies for the generation of customized animals for specific experiments were presented. It was agreed that these should be freely available. However, individual scientists and institutes should evaluate whether it is worth adopting a new and complicated technique. Since the process of setting up complex protocols may well lead to the use of high numbers of animals, investigators should consider collaborating with colleagues who perform similar experiments at large scales.

Ethical considerations let us come to the understanding that there is an intrinsic value of life. We found that it is for this reason that it is morally wrong to kill more animals than absolutely necessary. Biomedical science is tasked with producing answers to pressing questions on the molecular functions of life and disease and finding new cures. It was pointed out that the principles of the 3R’s have to be respected at all times, but a number of animal experiments are indispensable. In this context, it is unavoidable to breed animals that are not used for these experiments, but it is important to ensure that their numbers are kept to a minimum.

Boris Jerchow
Member of ISTT’s Executive Council
October 23, 2013

List of participants and affiliations, excluding those who were unable to send permission for disclosure:

van der Broek, Frank, NVWA, The Netherlands; Aleström, Peter, The Norwegian Zebrafish Platform, Norway; Benavides, Fernando, University of Texas, USA*; Bussell, James, Wellcom Trust Sanger Institute, UK*; Chrobot, Nichola, MRC Harwell, UK; van Es, Johan, Hubrecht University, The Netherlands; Fentener van Vlissingen, Martje, Erasmus MC, The Netherlands; Hendriksen, Coenraad, InTraVacc, The Netherlands; Hohenstein, Peter, Roslin Intitute, UK*; Krimpenfort, Paul, NKI, The Netherlands; Morton, David, UK; Prins, Jan-Bas, LUMC, The Netherlands; Raspa, Marcello, EMMA, Italy*; Tramper, Ronno, Consultant, The Netherlands; van der Valk, Jan, NKCA; Wilbertz, Johannes, Karolinska Institutet, Sweden*; Ohl, Frauke, Utrecht University, The Netherlands; Pool, Chris, KNAW, The Netherlands; Witler, Lars, Max-Planck Institute Mol. Gen., Berlin, Germany*.

* ISTT members

Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)

Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands (Picture kindly provided by Fernando Benavides)

Janet Rossant will be awarded the 10th ISTT Prize at the TT2014 meeting in Edinburgh

Monday, October 21st, 2013
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Janet Rossant (Hospital for Sick Children, Toronto, ON, Canada) will be awarded the 10th ISTT Prize at the TT2014 meeting in Edinburgh (picture kindly provided by JR)

Janet Rossant (Hospital for Sick Children, Toronto, ON, Canada) will be awarded the 10th ISTT Prize at the TT2014 meeting in Edinburgh (picture kindly provided by JR)

The International Society for Transgenic Technologies (ISTT) is pleased to award the 10th ISTT Prize to Professor Janet Rossant, Senior Scientist in the Developmental & Stem Cell Biology Program, Chief of Research at The Hospital for Sick Children, Toronto, Ontario, Canada; University Professor at the University of Toronto; Deputy Scientific Director of the Canadian Stem Cell Network; and Professor in the Departments of Molecular Genetics, Obstetrics / Gynaecology and Paediatrics at the University of Toronto. The ISTT Prize is given to an investigator who has made outstanding contributions to the field of transgenic technologies. As a world leader in developmental biology, and someone who has made seminal contributions to our field, Professor Janet Rossant will receive the award at the next Transgenic Technology meeting (TT2014), which will be held in Edinburgh (Scotland, UK) on October 6-8, 2014.

In awarding this prize to Dr. Rossant, the ISTT Prize committee acknowledges her many fundamental contributions to the science and technology of manipulating early pre-implantation mouse embryos and their instrumental role in our current understanding of mouse genetics and developmental biology. Her work on embryonic stem cell biology, blastocyst-derived cell lineages, and the mechanisms of cell-fate decisions in the early mouse embryo have been fundamental in deciphering how embryo-derived stem cells can be maintained and differentiated. Furthermore, her personal contributions in all of these areas have facilitated the development of the mouse transgenesis tools and methods used daily by many ISTT members.

Along with her active participation in many other related scientific and educational events, the ISTT Prize committee wishes to highlight Dr. Rossant’s most generous dedication to the dissemination of mouse transgenesis techniques among young scientists and technologists, through her pivotal role in the organization of the Great Lakes Mammalian Developmental Biology Meeting series in Toronto for more than thirty-five years, and her participation in the two classical CSHLP videos on techniques of mouse transgenesis (1989) and ES cells (1993), still regularly used today, and available as digital videos from the ISTT web site for its members.

Dr. Rossant was among the few pioneers who established, mastered and disseminated the technique of introducing targeted mutations into genes using mouse ES cells, leading to the generation of knockout mice and using them both to understand fundamental developmental processes and as animal models of human disease. Dr. Rossant’s interest in following the progression of mouse development from embryo to adulthood has led her to study stem cells from which individual tissues are derived during development. Her current research interests are focused on understanding the genetic control of normal and abnormal development in the early mouse embryo using both cellular and genetic manipulation techniques. Her interests in the early embryo have increased our understanding of the trophectoderm, and the discovery of a novel placental stem cell type, the trophoblast stem cell. Her current goal is to understand the genetic and cellular networks involved in blastocyst formation. By understanding how normal mammalian development occurs, she aims to understand how to regulate pluripotency using human ES or iPS cells in future therapeutical applications.

Dr. Rossant was born in Chatham (UK) in 1950. She obtained her B.A. and M.A. in Zoology at the University of Oxford, UK, in 1972, followed by her PhD in Developmental Biology in 1976 at the University of Cambridge, UK, working in Richard Gardner’s laboratory. While she was an undergraduate student in Oxford she attended a few courses taught by John Gurdon and became fascinated by developmental biology. Since 1977 she has been working in Canada, first at Brock University in St Catharines as an Assistant Professor and later as Associate Professor at the University of Toronto, where she was appointed Professor in 2001. Since 1985 she has been working in Toronto, first at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, until 2005, and then at the Hospital for Sick Children, where she now leads her research group.

In addition to being awarded the 10th ISTT Prize for Transgenic Technologies at the TT2014 meeting by the International Society for Transgenic Technologies, Dr. Rossant has been recognized for her contributions to science with many other awards, including the Killam Prize for Health Sciences, the March of Dimes Prize in Developmental Biology, the Conklin Medal from the Society for Developmental Biology, the CIHR Michael Smith Prize in Health Research (Canada’s most prestigious health research award), the Excellence in Science Award from the Federation of American Societies for Experimental Biology, the National Cancer Institute of Canada /Eli Lilly Robert L. Noble Prize for excellence in cancer research, and the McLaughlin Medal from the Royal Society of Canada. She has twice been named a Howard Hughes International Scholar, and is a recipient of the Ross G. Harrison Medal (lifetime achievement award) from the International Society of Developmental Biologists. She is a Fellow of the Royal Societies of both London and Canada, and is a foreign Associate of the US National Academy of Science.

Her highly prolific career includes over 340 publications, including some milestone achievements in the fields of early mouse embryogenesis and stem cell biology.

Her first few papers, dating from 1975, already addressed what would be a recurrent research topic in her career, namely, investigating the cell-fate determination of the inner cell mass of mouse blastocysts, from which embryonic stem cells are derived. She worked with Andrzej K. Tarkowski, the pioneer in producing mouse chimeras, and published with him a 1976 Nature paper on the development of haploid mouse blastocysts from bisected zygotes. She worked in 1979 with Richard Gardner, another pioneering researcher in pre-implantation embryos, investigating the cell fate of inner cell mass cells. Her studies resulted in the completely normal development of interspecific chimeras in mammals in 1980, using two species of mice. Since the early 1980s she showed an interest in the trophectoderm cell lineage and its relevance in mammalian pre-implantation embryos and in the generation of the placenta and other extra-embryonic cell lineages. Since then she has collaborated with many other key scientists in the fields of mouse transgenesis, mouse embryogenesis and stem cells, including V. Papaioannou, R. Balling, A. McLaren, A. Bernstein, A. Nagy, A. Joyner, W. Skarnes, A. Gossler, KS. Zaret, TW. Mak, A. Pawson, A. McMahon, R. Jaenisch, EM. DeRobertis, P. Soriano, D. Melton, R. Kemler, P. Avner, S. Yamanaka and Q. Zhou, among many others, and has contributed extensively in the areas of mammalian vascular development, trophoblast-derived cell lineages, and early mouse embryogenesis, as well as in the development of large-scale collaborations such as the International Gene Trap Consortium, The International Knockout Mouse Consortium, and the International Stem Cell Initiative, for establishing benchmarks for human stem cell research. Dr. Janet Rossant is also the current President of the International Society for Stem Cell Research (ISSCR).

Dr. Rossant joins the list of previously awarded scientists with the ISTT Prize, consisting of (in descending chronological order): Allan Bradley (2013), Ralph L. Brinster (2011), A. Francis Stewart (2010), Brigid Hogan (2008), Charles Babinet (2007), Andras Nagy (2005), Qi Zhou (2004), Kenneth J. McCreath (2002), Teruhiko Wakayama (2001). All ISTT Prize winners are given Honorary Membership in the ISTT and a unique sculpture representing a silver mouse blastocyst created by the Hungarian artist Mr. Béla Rozsnyay.

The ISTT Prize Committee includes the ISTT President and Vice-President, the CEO of genOway (the company generously sponsoring the award), and previous ISTT Prize awardees.

Selected references from Janet Rossant’s lifetime achievements:

Download the 10th ISTT Prize press release to be awarded to Janet Rossant

Additional sources of information for Janet Rossant’s biography:

 

 

Livestock and other non-rodent genetically modified animal resources available from the ISTT web page

Monday, September 2nd, 2013
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Livestock and other non-rodent genetically modified animal resources available from the ISTT web page

Livestock and other non-rodent genetically modified animal resources available from the ISTT web page

There is life beyond mice and rats, there are many additional interesting and useful genetically-modified animal models beyond those made using rodents. Rodents are great animal models for genetic/genomic analyses and for the first preliminary experimental tests. However, larger mammals are more suitable to study most human diseases and to develop therapies and treatments. Likewise, other vertebrates, such as chicken and fish, are also very interesting and useful to develop applications in animal biotechnology. At the International Society for Transgenic Technologies (ISTT) we have an increasing population of members working with all these other non-rodent genetically modified animals. The reference meeting in this area is the Transgenic Animal Research Conference (TARC), organized by ISTT Member James Murray (UC Davis, CA, USA) every two years, in August. The ISTT has had the pleasure to co-sponsor the last three editions of this conference series, in 2009, 2011 and 2013. In addition, in response to an increased interest by new ISTT members, a session devoted to non-rodent transgenic animals has been regularly scheduled in the last TT meetings (i.e. TT2011 and TT2013).

Now, from the ISTT web site, we would like to contribute disseminating and informing about all these other non-rodent transgenic animal models by launching a new web page with a collection of available resources for livestock and other non-rodent genetically modified animals.  This page contains links to several academic and private institutions working with non-rodent transgenic animals. The list is not exhaustive and will be progressively updated and expanded with your suggestions and recommendations. Hence, if you are working in this field and your web page is not yet included in this web page, please contact us at webmaster@transtechsociety.org and we will correct, modify or add your suggested information. Thanks in advance for your expected collaboration!.

Meeting report: IX Transgenic Animal Research Conference. Granlibakken Conference Center, Tahoe City, California, USA, 11-15 August 2013

Tuesday, August 20th, 2013
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Lake Tahoe, CA, USA

Lake Tahoe, CA, USA

The IX Transgenic Animal Research Conference, organized by ISTT member Jim Murray (UC Davis), was held last week at the Granlibakken Conference Center, Tahoe City, California, USA. The unique and beautiful location of this meeting series, by Lake Tahoe, in Northern California, surrounded by woods and mountains (and sporting chipmunks and bears), triggered its magic again and, hence, this ninth TARC was a rewarding success. The conference was attended by about 100 delegates from academia and industry, representing groups primarily interested in the generation, analysis or marketing of non-rodent transgenic animal models, as well as regulators and representatives from governmental agencies. This conference was co-sponsored by the ISTT.

The meeting started with a most passionate keynote address by Matt Wheeler (University of Illinois, USA) who reminded us about our responsibility and the mission we all have as biotechnologists to improve the efficiency of food production in cattle, pigs, and also poultry (as adequately reminded by Helen Sang [Roslin Institute, UK]) , using our unique genetic tools and techniques. Dr. Wheeler provided a number of striking figures to highlight the extraordinary need for food in the near future: “estimates have suggested that we will need to increase our current food production by 70% by 2050. This means that we will have to produce the total amount of food each year that has been consumed by mankind over the past 500 years”. He also expressed regret at how transgenic large animal programs were declining in the US, in part due to the lack of trust in a regulatory process that has been witholding the approval of some early transgenic animals. One major example of this is the ongoing saga of the fast growing AquAdvantage transgenic salmon, produced by AquaBounty, not yet approved, more than 20 years after being first generated. Finally, he openly referred to the unacceptable cost for the world, of not using the most advanced genetic engineering techniques to improve food production. He concluded that “hunger is a curable disease”.

Scott Fahrenkrug (Recombinetics Inc., USA) continued with a most interesting talk describing how the new gene editing tools (i.e. TALENs) can be applied for direct livestock genetics. Using illustrative examples in pigs and cattle he demonstrated the efficient introduction of single and multiple subtle genetic changes, often found as rare alleles in some breeds and difficult to introduce in the animal of choice by standard genetic breeding program, where the segregation of traits would require tens of thousands of animals and many generations. This first of several talks on genome editing tools was followed by that of Emmanuelle Charpentier (Helmholtz Center for Infection Research, Germany), one of the pioneers and discoverer of the CRISPR-Cas9 system in bacteria, and its application for the efficient gene edition in mammals. She suggested that new applications will come from the use of new variants of the RNA-guided Cas9 endonuclease.

Emerald Bay, Lake Tahoe, CA, US

Emerald Bay, Lake Tahoe, CA, USA

The second session started with a talk by Daniel Carlson (Recombinetics Inc., USA), who gave technical details of the experiments described briefly by Scott Fahrenkrug, highlighting the factors that can influence success when attempting to precisely edit the genome of livestock species (pig and cattle) with TALENs. Next, Charlotte Brandt Sorensen (Aarhus University, Denmark) reported on the efficient genome engineering in pigs using both recombinant adeno-associated virus (rAAV) and TALENs in order to generate swine animal models of breast cancer and Type II diabetes. The session concluded with a technical lecture delivered by Colin Fox (Genentech, USA), on their approaches to systematically and efficiently genotype complex genetic alterations in transgenic animals affecting multiple alleles.

The third session was focused on the use of pigs for a variety of purposes. First, Kevin Wells (University of Missouri, USA), reported on their advances in a gene stacking project, where the use of phiC31 integrase and its corresponding target sites was evaluated, in parallel to standard homologous recombination approaches, for the efficient cointegration of multiple alleles at discrete genomic locations. The session was completed with talks from two German groups, where Nikolai Klymiuk (Ludwig-Maximilian University, Germany) and Angelika Schnieke (Technische Univ. Muenchen, Germany) shared their progress in xenotransplation and the modeling of cancer disease in pigs, respectively.

The fourth session, on the conference’s second day, started with a talk by Liangxue Lai (Guangzhou Institutes of Biomedicine and Health, China) reporting on their progress with a series of pig models of human degenerative diseases including Parkinson, Ataxia (ALS), Huntington and Alzheimer. Liangxue Lai had also participated as invited speaker at the TT2013 meeting in Guangzhou, held previously this year. Chuck Long (Texas A&M University, USA) presented work from his lab using lentiviral transgenes in cattle to knock-down the myostatin locus by RNA-interference. He also reported on a new model for muscle steatosis (marbling) in pigs. The session ended with a totally different animal system: chickens and avian primordial germ cells (PGCs), delivered by Mike McGrew (Roslin Institute, UK). Mike reported progress made in his lab to establish efficient conditions to culture chicken PGCs and his attempts to generate inducible knock-down of target genes using transposons and the TET-system.

Lake Tahoe, CA, USA

Lake Tahoe, CA, USA

The fifth session, with two talks, was entirely devoted to further evaluate risk assessment on the transgenic goat model producing lysozyme in milk, generated by Jim Murray and collaborators at UC Davis. First, Elizabeth Maga (UC Davis, USA) systematically analyzed whether there were any unintended effects associated with the mammary-specific expression of the lysozyme transgene in the host (lactating goats) and in a non-targeted organism (kid goats consuming the milk from transgenic goats). Even though they found some statistically significant differences among the many tests conducted, these were considered of no biological relevance, more due to time of expression and not due to the presence of the transgene. She concluded that there were no unintended effects as revealed in these analyses. Second, Caitlin Cooper (UC Davis, USA) shared her analysis on the effects of consumption of milk containing lactoferrin (from transgenic cows) and/or lysozyme (from transgenic goats) on the intestinal health in young pigs. Her studies concluded that lactoferrin and lysozyme exhibit both shared and unique mechanisms and highlighted the relevance of dosage in the positive effects observed in the intestinal villi architecture and the overall balance of several cells of the immunity system in the gut.

The sixth session presented two different but equally-interesting advances obtained by two agrobiotech companies. First, AgResearch’s researcher Goetz Laible (New Zealand) described their success in reducing the contents of beta-lactoglobulin (BLG) in ovine and cow milk, hence aiming to produce a less allergenic milk for eventual human consumption. They tested their strategy using RNA-interference in mice, with the help of some transgenic mice producing BLG in their milk. Finally, they generated a cow producing milk with reduced allergens. Next, Benjamin Schusser (Crystal Bioscience, Inc., USA) shared their advances towards producing therapeutic monoclonal antibodies against human proteins in chickens. In this regard, he documented the creation of the first chicken knockouts, for the IgL and IgH loci, by inserting the corresponding variable regions of human Ig loci.

The seventh session was also devoted to advances in chicken genetic engineering. Tim Doran (CSIRO, Australia) began with a description of an alternative way of genetically modifying chicken PGCs with transposon-type transgenes by direct in vivo transfection, thus avoiding the need to isolate, culture and reinsert these cells in host chicken embryos. This talk was followed by that of Mark Tizard (CSIRO, Australia), illustrating how the use of innovative RNA-interference approaches could be used for efficient trait control and disease resistance in poultry.

Lake Tahoe, CA, USA

Lake Tahoe, CA, USA

The conference’s last day started with three new large animal models for human diseases. First, Irina Polejaeva (Utah State University, USA) described her transgenic goat models that overexpress the profibrotic factor TGF-ß1 in cardiomyocytes, designed to study the relationship between cardiac fibrosis and atrial fibrillation. Next, Chris Rogers (Exemplar Genetics, USA) presented pig models for human hypercholesterolemia and atherosclerosis generated by disrupting the LDL receptor gene in the pig genome. The LDLR deficient pigs are currently being used to test new cholesterol-lowering drugs and to develop detection and treatment strategies for atherosclerosis. The session finished with a talk by Zhong Wang (University of Michigan, USA) and their new approaches to study heart development and regeneration in pigs.

The eighth session was devoted to the progress of animal products generated using biotechnology with regard to regulation and the expected path to market, once the product is investigated, validated and eventually approved by the relevant regulatory bodies. This process was described by Ronald Stotish (AquaBounty Technologies, USA), who shared the extremely long and as-yet unsuccessful attempt to obtain required FDA approval for marketing the AquAdvantage salmon. This fast-growing transgenic fish can grow to expected market size in half of the time required for non-transgenic salmon using standard aquaculture procedures. The apparent science-based regulatory process has been repeatedly interrupted by not only anti-technology groups but other groups with obvious political and economic interests conflicting with the marketing of these salmon. More than 20 years have passed since this transgenic salmon was first generated, and yet, after numerous scientific studies demonstrating that this product is as safe as non-transgenic salmon and after concluding that it does not pose a significant threat for the environment, the final approval by the FDA has not been issued. The seminar on the transgenic salmon issue was followed by a nice summary talk by Alison van Eennennaam (UC Davis, USA) where she presented how the regulation of genetically-modified animals is interpreted in different countries/continents, such as US, Europe or Australia, and the consequences these definitions have on the overall regulatory process aiming to obtain a permission to market a given transgenic animal or a product derived from them. Furthermore, she challenged the current regulatory scenario with the new gene editing tools (i.e. ZFNs, TALENs, or CRISPRs-Cas) where, in most cases, the genetic alterations leave no specific footprints and are undistinguishable from other similar genetic alleles that can be found in the nature, among the different breeds of a given species. Knowing in advance whether these precise genetic engineering processes will or will not be regulated through the current laws or whether they would require an adaption of current norms is of paramount importance for the progress of the animal biotechnology field.

The final session held two great but totally different talks. First, Derric Nimmo (Oxitec Inc., UK) described their elegant and innovative solution to efficiently down-regulate wild populations of mosquitoes (Aedes aegypti) This mosquito species survives by constantly feeding on human blood, and also serve as a vector to transmit serious diseases such as dengue or yellow fewer. He reported their approach using their RIDL strategy (Release of Insects with Dominant Lethality). The mechanism is based on a modified TET-off system where the tTA-VP16 activator is strongly expressed under several tet-op sequences unless the effector, Doxycycline (Dox), is provided in the diet. Hence, male transgenic mosquitoes can be raised in the laboratory, where the expression of the transgene is prevented with Dox, but, upon release in the wild, the lack of Dox triggers the expression of the transgene and the accumulation of the powerful transcriptional activators which cause irreversible damage to transgenic male mosquitoes, rending them sterile. Release of these sterile males and their subsequent mating with female populations is an efficient way to downsize wild mosquito populations. Approved open field tests have been already conducted in Cayman Islands, Malaysia and Brazil with success. The company is currently awaiting approval by the FDA and other equivalent agencies in order to apply their strategies in the US and other countries. This talk also illustrated the positive and rewarding effect accomplished by investing in informing people, affected populations, hospitals, governments, schools, etc… about this biotechnological approach to reduce disease-transmitting mosquitoes, which resulted in increased acceptance by the local populations. This community engagement approach appears to be the most promising and effective manner of gaining society’s acceptance for genetically-engineered animals and/or products.

Emerald Bay, Lake Tahoe, CA, USA

Emerald Bay, Lake Tahoe, CA, USA

The honor of the traditional concluding talk was given this time to Bruce Whitelaw (Roslin Institute, UK) with the challenge to envisage what the fourth decade would bring, after three decades of genetically engineered animals. After referring to the predicted needs for safe and more efficient food that this planet will need in the immediate future, Bruce divided the four decades as follows, identifying in each of them some major technological milestones: 1984-1993 (decade of the first transgenic animals produced by standard DNA pronuclear injection); 1994-2003 (decade of nuclear transfer, when Dolly was created and laid the foundation to generate many cloned and genetically-engineered mammals, using a technique currently referred as SCNT. At this point, Bruce kindly offered a tribute to the work done by Keith Campbell, instrumental in the creation of Dolly, who recently passed away); 2004-2013 (decade of a revolution in technologies including the use of lentivirus, transposons, SMGT, bird PGCs, ZFNs, TALENs and CRISPRs, and also, the decade of the first large animal models of human disease being effectively produced and tested). For the fourth decade, 2014-2023 Bruce speculated that the balance will re-equilibrate efforts and investments in both agricultural and biomedical sciences, after two decades where the genetic-engineering of animals was mostly dominated by projects and applications in biomedicine. He left us with the following thought: “The 4th decade of GE livestock is going to be good for those who work with this technology and for those – both man and animal – who benefit from it”.

Emerald Bay, Lake Tahoe, CA, USA

Emerald Bay, Lake Tahoe, CA, USA

All participants left home on August 15, after having enjoyed yet another fantastic conference put together by Jim Murray, who must be praised for his unrelenting commitment to this great meeting series, where the generation and application of non-rodent transgenic animals are discussed in depth, before, during and after the talks.
The next TARC meeting, the 10th Transgenic Animal Research Conference, will be held, at the same place, on August 9-13, 2015. We would encourage you to experience these meetings first hand, (and not through these meeting reports). Please make sure to book these dates on your agenda and not miss the next meeting by beautiful Lake Tahoe.

Lluis Montoliu & Jan Parker-Thornburg

IX Transgenic Animal Research Conference, Tahoe City, CA, USA, 11-15 August 2013

Wednesday, February 13th, 2013
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IX Transgenic Animal Research Conference, Tahoe City, CA, USA, 11-15 August 2013

IX Transgenic Animal Research Conference, Tahoe City, CA, USA, 11-15 August 2013

The International Society for Transgenic Technologies (ISTT) has decided, once again, to co-sponsor the IX Transgenic Animal Research Conference, hosted by the Department of Animal Science, UC Davis, and organized by ISTT Member Prof. James D. Murray. This conference will be held at the Granlibakken Conference Center, in Tahoe City, CA, USA, on 11-15 August 2013. This is a classical conference, most complementary to the TT meeting series, and specifically devoted to basic and applied projects, research and technical developments using non-rodent genetically modified animals. The ISTT is proud to have supported the two previous UC Davis Transgenic Conferences in Tahoe held in 2009 and 2011.

According to the conference web site:  This is the ninth international meeting hosted by UC Davis to bring together representatives from the leading laboratories worldwide doing cutting edge work on transgenic research in non-murine animals, including livestock, fish and poultry species. The previous meetings were each attended by up to 160 participants from 12 to16 different countries throughout the globe. Each conference, in addition to reviews and papers on transgenic animals, included presentations covering technical developments in areas such as nuclear transfer-based cloning, cell transformation, vector design, and nuclease-directed gene insertion that affect the production of transgenic animals. Oral presentations are by invitation, with participants encouraged to contribute poster presentations. The upcoming conference will again focus on state-of-the-art science in the field of transgenic research. Presentations will address cutting-edge methodology, technical improvements, and current progress towards producing transgenic animals for biomedical and agricultural applications. The intent of these meetings is to bring together scientists to discuss progress, problems, and potential application of transgenic technology for animal applications. The meeting will consist of invited presentations and submitted posters. Two afternoons from noon to 4 p.m. and one evening will be free to allow for small group interactions and to take advantage of the great natural beauty and recreational activities in the Lake Tahoe area.

Already appointed and confirmed Speakers include:

  • Matt Wheeler (Illinois) – opening talk
  • Bruce Whitelaw (Edinburgh) – closing talk , ISTT Member
  • Scott Fahrenkrug (Minnesota) – TALENS in livestock
  • Emmanuelle Charpentier (Germany/Sweden) – CRISPR RNA-programming technology
  • Caitlin Cooper (Davis) – feeding hLZ and hLF milk to pigs
  • Hongbin He (China) – FMDV resistance
  • Angelika Schnieke (Germany) – cancer models in pigs
  • Chuck Long (A&M) lentiviral production of livestock
  • Irina Polejaeva (Utah) – tg goat cardiovascular models
  • Goetz Laible or Stefan Wagner (NZ) – KO of beta-lactoglobulin and transduction of the mammary gland
  • Rob Etches (Crystal Biosciences) – heavy chain KO chickens
  • Yonglun Luo (Alun) (Denmark) – adeno-assoc HR + talens / BCRA-1
  • Mike McGrew (Roslin) growing and modifying avian primordial germ cells, including transposons
  • Tim Doran (Aust) Virus disease resistant transgenic poultry and fish
  • Derek Nimmo (UK) – TG mosquito for control of dengue fever
The complete registration packet for this IX TARC conference includes: conference registration fee, four night’s accommodation at Granlibakken, all meals, refreshments, receptions and ground transportation from Davis or Reno (if needed) (USD 1,600). ISTT Members are entitled to a reduced registration fee (USD 1,550). Registrations received after June 14, 2012 are NOT guaranteed.

7th Workshop on Innovative Mouse Models (IMM2013), Leiden, The Netherlands, 13-14 June 2013

Tuesday, February 12th, 2013
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7th Workshop on Innovative Mouse Models (IMM2013), Leiden, The Netherlands, 13-14 June 2013

7th Workshop on Innovative Mouse Models (IMM2013), Leiden, The Netherlands, 13-14 June 2013

The International Society for Transgenic Technologies (ISTT) has agreed to co-sponsor the 7th Workshop on Innovative Mouse Models (IMM2013), which will be held at the Leiden University Medical Center (LUMC), in Leiden, The Netherlands, on 13-14 June 2013.  This will be the third consecutive edition of this meeting series that is granted with the co-sponsorship of the ISTT, after the IMM2011 and the IMM2009 editions, due to its interest and relevance for the community of researchers using genetically-modified mice. The IMM2013 workshop is organized by: Jos Jonkers (NKI-AVL, Amsterdam, The Netherlands), Paul Krimpenfort (NKI-AVL, Amsterdam, The Netherlands), Werner Mueller (University of Manchester, Manchester, United Kingdom), Hein te Riele (NKI-AVL, Amsterdam, The Netherlands), Els Robanus-Maandag (LUMC, Leiden, The Netherlands), Marian van Roon (VU, Amsterdam, The Netherlands and ISTT Member) and Sjef Verbeek (LUMC, Leiden, The Netherlands and ISTT Member).

According to the IMM2013 workshop web page: The primary goal of this two-day workshop is to bring together a diverse group of scientists interested in advanced genome alteration approaches in the mouse, including key developers of emerging technologies as well as researchers who wish to apply and assess these new approaches. The IMM2013 workshop will encourage an in-depth and unvarnished discussion of these technologies and novel developments. This 2-day workshop will have a mixture of invited speakers and selected presentations. Keynote lectures will be given by:

  • Anton Wutz (UK) haploid ESC
  • Haoyi Wang (US) iPS / TALENs
  • Bill Skarnes (UK) high throughput TALENs
  • Ben Davis (UK) docking site/ new recombinases
  • Yann Herault (France) Cre transgenic mice
  • Kevin Brindle (UK) MRI
  • Mathijs Verhagen (NL) large scale phenotyping
  • B Kappes (US) TALENs
  • Zoltan Ivics (Germany) Transposons
Registration will open soon. ISTT members will be entitled to a reduced registration fee.

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