PhICSI: injecting sperm into a one cell mouse embryo

Mice born by phICSI apper healthy and are able to produce at least two generations of offspring

Suzuki T. et al. Nat. Commun.7:12676 (2016)

Suzuki T, Asami M & Perry ACF. Scientific Reports (2014)

Founder (F0, left) and F1 offspring produced by Cas9-mediated mII editing of the Tyr locus. Editing to produce founders was performed in C57BL/6. Yellow arrow, mosaic; red arrows, apparently non-mosaic mutants. The F1 litter was produced by crossing a black coat-colour female founder with a CD1 male; the founder carried a germline Tyr mutation confirmed by sequencing, to produce white coat-colour pups (indicated with red arrows in F1, right).

 

[August 21st, 2018] Tony was pleased to meet presenters for a BBC Radio 1 Stories, "DNA+: Beauty", BBC iPlayer programme, out on 21.08.18, although he was talking about preventing disease, not beauty: 

https://www.bbc.co.uk/iplayer/episode/p06gx2kf/radio-1-stories-dna-beauty#    

[July 3rd, 2018] A novel switch to control genome editing

A biological switch that reliably turns protein expression on at will has been invented by us together with group of Dr Tsai (Cardiff University). The switch enables control of genome editing tools that might one day regulate cascades of desired genetic changes through entire populations.
This new switching method should work for any protein in any species and uses a cheap, non-toxic amino acid as the control switch - the 'on' mode requires the presence of an amino acid called BOC.

<https://www.nature.com/articles/s41598-018-28178-3>

[January 31st, 2018]  Festive of Genomics

'Tony is honoured to have been invited to speak at the 2018 Festival of Genomics at ExCeL, London, on January 31st, when he will discuss heritable human genome editing'

http://www.festivalofgenomicslondon.com/speakers/tony-perry?&azletter=T&searchgroup=libraryentry-speakers

[19th Dec 2017] University nominated for animal research openness award

We contributed for the nomination to ‘Media Engagement’ award at the recent Understanding Animal Research (UAR) Openness Awards.

The annual awards recognise best practice in openness around animal research from signatories of the Concordat on Openness on Animal Research.

The University was nominated for its media work around a discovery by Dr Tony Perry and his team.

The story was the focus of major international media attention. Working with the University press office Dr Perry and colleagues held a press conference at the Science Media Centre in London, and then participated in numerous radio, TV and print media interviews over several days.  TV cameras were also permitted into the University’s animal research facility and Dr Perry’s labs to film where and how the work took place. http://reut.rs/2kmIkly

Dr Perry said: “We wanted to communicate our ground-breaking research to the public and knew it was really important to be clear the research took place in mice. This not only gave people an accurate picture of the story, but let them know animal research was necessary for this type of science.

“It’s great to have been nominated for the award and see Bath demonstrating commitment to the Concordat on Openness on Animal Research.”

http://www.bath.ac.uk/news/2017/12/19/animal-openness-award/

[9th Nov 2017]

Humans 2.0: the lab contributes to a review on mitochondrial replacement therapy in November’s issue of Nature Biotechnology

https://www.nature.com/articles/nbt.3997

https://www.nature.com/articles/nbt.4019

[TEDx Talk]

Tony's talk can be seen bellow now!

https://www.youtube.com/watch?v=0HsFA5350Rw

[Mar 2017]

Post-doctoral research associate position

A Research Council-funded postdoctoral position is available for 3 years in the laboratory of Dr Tony Perry. The successful candidate will be a key member of the laboratory working on mouse early embryos in the beautiful city of Bath, near London, Oxford and Cambridge.

We recently showed that mouse parthenogenotes support full development (Nat. Comm.) and developed a novel method for genome editing during fertilization (Sci. Rep.).

You will have a strong research background in mouse embryology, preferably with experience in piezo-actuated micromanipulation, and a PhD in a relevant subject area. Experience in molecular techniques would be a distinct advantage.

This post is offered on a full-time, fixed-term (36 months) contract, and is expected to start on or soon after 1st July, 2017. We encourage applications from overseas.

Informal enquires are welcome and should be directed to Dr Tony Perry (perry135@aol.com).

Technician positions

Research Council-funded technician position available to work on the molecular biology of mouse early embryos in the laboratory of Dr Tony Perry in the beautiful city of Bath, near London, Oxford and Cambridge.

We recently showed that mouse parthenogenotes support full development (Nat. Comm.) and developed a novel method for genome editing during fertilization (Sci. Rep.).

You will have experience in molecular techniques including one or more of molecular cloning, immunoblotting and qPCR. Experience handling mice would be an advantage and there will be authorship opportunities.

This post is offered on a full-time, fixed-term contract (18 months in the first instance with 6 months probation period), and is expected to start this summer, 2017. Informal enquires are welcome and should be directed to Dr Tony Perry (perry135@aol.com).

[30th Sep 2016]

On Sept 30, the Nuffield Council on Bioethics Working Group on Genome Editing, of which Tony was a member, published its Platform Report, which can be found at

http://nuffieldbioethics.org/project/genome-editing/

[13th Sep 2016]

We have developed a method of injecting mouse parthenogenotes with sperm that allows them to become healthy offsprings with a success rate of up to 24 per cent of its control. This compares to a rate of zero per cent for parthenogenotes or about two per cent for nuclear transfer cloning.

Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes

Nat. Commun. 7:12676 doi:10.1038/ncomms12676

[21 June 2016]

Tony join the reconvened Human Fertilisation & Embryology Authority (HFEA) panel to consider the safety and efficacy of mitochondrial donation technique

[23rd May 2016]: Why? When? Who? Report of workshop on genome editing and public dialogue now published

(Nuffield Council on Bioethics) http://nuffieldbioethics.org/news/2016/why-when-who-

report-of-workshop-on-genome/

[May 2016] Two positions in our lab are available.

1) An MRC-funded postdoctoral position

2) MRC-funded technician position

[18th Feb 2016]: Crazy for CRISPR: Tony talks to the Naked Scientist

www.thenakedscientists.com/HTML/podcasts/genetics/show/20160214/

[9 Dec 2015]

The 2015 anuual conference of the Progress Educational Trust (PET)

From Three-Person IVF to Genome Editing: The Science and Ethics of Engineering the Embryo

Tony contributes to the meeting as a speaker

"Festive Christmas Presents and Genomic CrispCas Presence: The Strategic Application of Scissors and Tape"

An account of the conference may be found bellow.

"www.progress.org.uk/conference2015"

[12 May 2015]

CRISPR germline engineering—the community speaks

Tony contributes to a potpourri of comments by the scientific community on germline engineering in May's Nature Biotechnology.

Nature Biotechnology 33, 478–486, (2015)

http://www.nature.com/nbt/journal/v33/n5/full/nbt.3227.html?WT.ec_id=NBT-201505

[10 May 2015]

Crispr: is it a good idea to ‘upgrade’ our DNA?

The lab's work on genome editing features prominently in a nice piece by Zoë Corbyn in the UK Observer.

http://www.theguardian.com/science/2015/may/10/crispr-genome-editing-dna-upgrade-technology-genetic-disease

[28 Apr 2015]

Council hosts scoping workshop on genome editing

On 22 April, Tony gave the lead-off presentation at the Nuffield Council on Bioethics workshop to identify the main issues raised by advances in genome editing. An account of the workshop may be found bellow.

"Nuffield Council on Bioethics"

http://nuffieldbioethics.org/news/2015/council-hosts-scoping-workshop-on-genome-editing/

[23 Dec 2014]

Asymmetric parental genome engineering by Cas9 during mouse meiotic exit

Mammalian genomes can be edited by injecting pronuclear embryos with Cas9 cRNA and guide RNA (gRNA) but it is unknown whether editing can also occur during the onset of embryonic development, prior to pronuclear embryogenesis. We here report Cas9-mediated editing during sperm-induced meiotic exit and the initiation of development. Injection of unfertilized, mouse metaphase II (mII) oocytes with Cas9 cRNA, gRNA and sperm enabled efficient editing of transgenic and native alleles. Pre-loading oocytes with Cas9 increased sensitivity to gRNA ~100-fold. Paternal allelic editing occurred as an early event: single embryo genome analysis revealed editing within 3 h of sperm injection, coinciding with sperm chromatin decondensation during the gamete-to-embryo transition but prior to pronucleus formation. Maternal alleles underwent editing after the first round of DNA replication, resulting in mosaicism. Asymmetric editing of maternal and paternal alleles suggests a novel strategy for discriminatory targeting of parental genomes.

[9 Aug 2013]

A caffeine fix for human nuclear transfer?

The August issue of Nature Biotechnology contains a News and Views commentary by Tony (1) on a recent report (2) of human cloning to generate nuclear transfer embryonic stem (ntES) cells. The long-anticipated success in human ntES cell generation rests on meiotic stabilization of occytes by caffeine prior to nuclear transfer, but the mechanisms remain arcane and the report really serves to highlight unknowns in the protocol. Tony's News and Views suggests what some of the unknowns might be and where there are addressable gaps relative to what is known about meiotic and epigenetic regulation in the embryos of model species such as the mouse. Although working with human oocytes and early embryos is fraught, it also presents a range of phenotypes not available to those working on animal models.

1.Perry, A.C.F. (2013). A caffeine fix for human nuclear transfer? Nature Biotechnol. 31, 717–719.

2.Tachibana, M. et al. (2013). Human embryonic stem cells derived by somatic cell nuclear transfer. Cell 153, 1228–1238.

[14 June 2012]

SCID pigs are here

The June 14, 2012 issue of Cell Stem Cell reports part of a long-standing collaboration between the laboratory of Dr Akira Onishi and the Perry lab (Suzuki et al., Cell Stem Cell 10, 753-758 [2012]). The paper reports the generation of severe combined immunodeficiency (SCID) pigs. SCID mice are well-established as models with which to analyse the behaviour of cancer and stem cells. Trouble is, some of the many biological differences between mice and humans are pretty much deal-breakers in the context of human pre-clinical comparisons; for instance, lab mice live for only two years, so they are of limited use for essential longer-term evaluation of stem cell transplantation therapies. By contrast, pigs are physiologically more akin to humans and live long enough (~10 years) to test better the efficacy of (for example) transplanted stem cells. The SCID pigs are the latest of several sophisticated approaches to genome manipulation Dr Onishi is taking to harness the biology of pigs in the development of human (and perhaps pig!) clinical strategies. In March, 2012, Tony became the first Westerner to visit the SCID pigs, in Tsukuba, Japan, when he took the picture shown of Dr Onishi.

[10 November 2011]

Yuami, England's first cloned mouse

The laboratory is pleased to announce the birth of England's first cloned mouse, Yuami (Japanese for 'taking a bath'). Yuami was one of two mice cloned by Dr Toru Suzuki from cumulus cell nuclei and was born on July 4th, 2011. Yuami was associated with placentomegally, which is characteristic of mouse clones, and is healthy and fertile. Yuami is believed to be the first adult cloned from an adult of any species in England.