Monthly Archives: June 2013

Breaking news: Mitochondria replacement therapy given green light

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Breaking news –  by Prof Bob Lightowlers

Professor Dame Sally Davies, the Governments Chief Medical Officer, has today given support to a change in the law that will allow the form of mitochondrial replacement therapy that is being pioneered here in Newcastle, has we mentioned before.

Its great news for any prospective mother with mitochondrial DNA disease who is concerned about transmitting the disease to their children.

Most media is covering this – BBC, Guardian, Telegraph – but if you are still confused, we thought it would be good to recap the essential points:

Electron micrograph of a cell (coloured blue) revealing part of the mitochondrial structure (orange) within. The entire length of the mitochondrion is about 5 micrometres.

– Mitochondria are crucial structures found in all cells in our body and they take our common foodstuffs such as fats and sugars and turn them into energy. They have their own genetic element, mitochondrial (mt) DNA. Much smaller than our chromosomes, mtDNA is essential for energy production.

– In 1988, scientists in the UK and US recognised that certain diseases were caused by mutations in mtDNA with the main disorders related to your muscle tissue and the brain.

– It is estimated that at least 1:10,000 people suffer from disorders associated with defects in mtDNA – that’s more than 6,000 people in the UK.

– Mitochondrial DNA is only transmitted to babies by their mothers. Unfortunately, as you inherit your mothers mitochondria, diseases caused by mtDNA mutations are inadvertently transmitted from the mother.

– Doug Turnbull, Director of the Wellcome Trust Centre for Mitochondrial Research (WTCMR) and I have wondered since the 1990s whether it would be possible to prevent the transmission of the faulty mtDNA from the mothers to their children by transferring the nucleous from an egg of the mother carrying these mtDNA mutations into a healthy egg whose nucleous had been removed, and then fertilise it

– Professor Mary Herbert, Doug and a group of us from the Mitochondrial Research Group were able to show that such a swap could be performed without any or very low levels of the defective mtDNA being transferred. Importantly, there was also no defect detectable in the reconstituted cells.

– In August 2012, the government asked the Human Fertility and Embryological Authority (HFEA) to find out what the general public thought of the procedure.  The results were collated  and the Human Fertility and Embryological Authority made a recommendation to Government. There was an overall support for the new technology with only 10% being fairly or strongly against the concept of mitochondrial gene replacement

To understand all the details and find out the whole story, see my post a while ago here.

The Wellcome Trust also has a very nice video explaining the science behind the news story:

 

 

Links

Wellcome Trust Centre for Mitochondrial Research http://www.newcastle-mitochondria.com/
Human Fertility and Embryological Authority (HFEA) http://www.hfea.gov.uk/index.html
HFEA mitochondria puclib consultation 2012 http://www.hfea.gov.uk/6896.html

 

Science Minister visits Centre for Bacterial Cell Biology

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by Dr Heath Murray 

On June 27 the RH David Willetts MP, Minister for Universities and Science, visited the Centre for Bacterial Cell Biology (CBCB) to hear about how research on bacteria can lead to: development of novel antibiotics, design of synthetic biological systems, and even understanding the origins of life on earth. Dr Heath Murray (CBCB & ICaMB) tells us more about this visit.

Mr. Willetts was given a guided tour of the new Baddiley-Clark building by the director of the CBCB, Prof Jeff Errington.

Jeff (left) outlines CBCB research to David Willetts (right), with Heath (middle back) paying close attention

Jeff discussed why he left Oxford University after 25 years to start the CBCB at Newcastle, the first Centre of its kind in the UK to provide a world-class facility in which to carry out fundamental research on bacterial cells. During the tour Jeff highlighted how the localised network of international researchers at the CBCB, working on biological problems in model bacterial organisms provides an unparalleled setting in which to exchange ideas and to benefit from related advances in microbial cell biology. While walking around Jeff noted how the open plan of the Baddiley-Clark building promoted interactions amongst the various research groups, thereby creating a uniquely stimulating environment for the scientists that work there.

This was a very fruitful visit with interesting discussions, as highlighted by Jeff: “I was impressed at how quickly the Minister picked up the key biological points we wanted to make, such as about how our work impacts on thinking about the origins of life!”

An image similar to those seen by David Willetts showing severe DNA segregation defect in a mutant Bacillus subtilis strain, observed using epifluorescent microscopy. (DNA: blue; origin of replication: green, cell membrane: red)

 

I then demonstrated the bespoke microscopes available within the CBCB to the Minister, highlighting how the small size of bacterial cells (only a few micrometers) makes microscopic analysis technically challenging and how the CBCB is utilizing state-of-the-art super-resolution microscopes to overcome this difficulty. I also explained how researchers use genetic engineering to fuse their “proteins of interest” to the Green Fluorescent Protein (GFP) from the jellyfish Aequorea victoria, thus creating tools to visualize the localization of proteins or nucleic acids within living bacterial cells using fluorescence microscopy.

 

Heath explains the potential applications of the research to the Science Minister

 

The Minister was keen to see the live demonstration of our fluorescent microscope and seemed amazed by how clearly the organization of the bacterial chromosomes was immediately apparent. He quickly appreciated that interfering with this process might have application in the development of new antibiotics.

 

 

We were all left with the clear feeling that Mr. Willetts enjoyed hearing about the science taking place within the CBCB and how this fundamental research provides insights crucial for the discovery and development of new antibiotics, as well as providing solutions to a wide range of industrial and environmental problems. “It was an interesting meeting – very reassuring to hear that the Minister is keen to make sure that Government continues to invest in Blue-Skies Research”, Jeff concluded.

 

ICaMB Research Update: Zenkin lab Science paper

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Congratulations to ICaMB and CBCB researchers Soren Nielsen, Yulia Yezenkova and Nikolay Zenkin and  who have a paper published in the prestigious journal Science today.

Nikolay Zenkin: RNA Polymerase researcher

There are three RNA Polymerases in Eukaryotic cells and although much attention focuses on the role of RNA Polymerase II, since it transcribes mRNAs from protein encoding genes, it is easy to forget that the majority of transcription in the cell is accomplished by RNA Polymerase III.  RNA Polymerase III (or Pol III as it is commonly known) is responsible for the synthesis of ribosomal 5S rRNA, tRNA and other small RNAs.

 

Soren’s paper, entitled “Mechanism of Eukaryotic RNA polymerase III Transcription” termination solves a long-standing mystery in the field of how transcriptional termination by RNA polymerase III takes place. Their study reveals an elegant scenario, in which co-transcriptional folding of highly-structured RNA polymerase III transcripts causes termination at the end of their genes. This mechanism ensures proper folding of the structural/catalytic RNAs synthesized by RNA polymerase III prior to RNA release. Analogies with bacterial termination suggest that this fundamental mechanism may have emerged before divergence of bacteria and eukaryotes.

Here is the Science Editor’s summary of the paper

It is as important to terminate any biological process as it is to start it. Transcription, copying information encoded in genes into RNA, requires accurate and timely termination. Nielsen et al. (p. 1577) present a mechanism for transcription termination by RNA polymerase III, the enzyme that synthesizes the majority of RNA molecules in eukaryotes. In this scenario, the folding of the RNA as it is transcribed by polymerase into a highly structured transcript causes termination at the end of its synthesis. This mechanism may serve as a control of proper folding of structural or catalytic RNAs synthesized by RNA polymerase III. Comparison with other organisms suggests that this mechanism emerged before divergence of bacteria and eukaryotes.

And here is the abstract of their paper

Gene expression in organisms involves many factors and is tightly controlled. Although much is known about the initial phase of transcription by RNA polymerase III (Pol III), the enzyme that synthesizes the majority of RNA molecules in eukaryotic cells, termination is poorly understood. Here, we show that the extensive structure of Pol III–synthesized transcripts dictates the release of elongation complexes at the end of genes. The poly-T termination signal, which does not cause termination in itself, causes catalytic inactivation and backtracking of Pol III, thus committing the enzyme to termination and transporting it to the nearest RNA secondary structure, which facilitates Pol III release. Similarity between termination mechanisms of Pol III and bacterial RNA polymerase suggests that hairpin-dependent termination may date back to the common ancestor of multisubunit RNA polymerases.

Links

Link to the Science paper: http://www.sciencemag.org/content/340/6140/1577.abstract

Nikolay Zenkin laboratory home page: http://www.ncl.ac.uk/camb/staff/profile/nikolay.zenkin#tab_research

Centre for Bacterial Cell Biology: http://www.ncl.ac.uk/cbcb/

Science magazine: http://www.sciencemag.org/

Link to the Science cover: http://www.sciencemag.org/content/340/6140.cover-expansion

IPA Update: What’s it like to work for Nature?

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By the IPA committee

Thursday 23rd May saw the IPA’s second Science Lives Seminar. Following on from our first talk about the realities of establishing an independent research group in academia, the IPA wanted to explore what else a post-doc can do. What are our alternative careers?

To start answering this question, we invited Dr Andrew Jermy, a senior editor at Nature, to give us a talk on his career in journal editing.


Postdocs waiting to hear either (a) how to publish their papers in Nature or (b) how to work for Nature

Dr Jermy’s talk started by illustrating his personal experience. Like all of us, he completed a PhD in the biological sciences field and then did two short post-docs before he decided to leave academia to start a career in editing, first at Nature Cell Biology, followed by  Nature Reviews Microbiology and now more recently at Nature. To achieve this, he used his networking skills as he had met someone currently working for Nature at conference. Hint, keep building up your contacts! It was very interesting for us all to understand the motivations that brought him to try a new and alternative career. “Getting bored of waiting for westerns to come out of the developer”, he repeated several times.  Maybe he is not the only one?

Dr Jermy also described the several different job entry levels possible at Nature, something that applies generally to many of the larger scientific journals.  We now have a much better idea of what working for a scientific journal actually entails and where we could slot in. He pointed out that in this kind of career you need a keen interest in all science, as well as being constantly on top of the cutting edge research in your specific editing field. The ability assimilate information quickly and handle up to 40-50 papers per month, while travelling to conferences and universities is also a must. On the other hand, Dr Jermy underlined that his job is not a simple 9-5 job.  However, he can work from home and with the advantage of a permanent position as well as opportunities for career progression, this can make his career more family-friendly than what we post-docs are used to. Ultimately, this career seems ideal for those post-docs who no longer enjoy working at the bench, but still enjoy the other aspects of scientific life, such as reading, writing and networking at conferences.

Andrew demonstrates the Nature ‘secret handshake’

There was however much more to Dr Jermy’s talk than the career side… he gave practical tips to post-docs who want (or maybe its better to say wish) to submit a paper to Nature; from the title to the covering letter, from the abstract to the “style” of writing. Dr Jermy made a clear point that the philosophy of the journal is not to bin 90% of the papers they receive, but to focus on helping the top 10% of the articles emerge and get published. Finally, did you know you can send a pre-submission enquiry to Nature, asking if your scientific results are of interest before going through the long and painful online submission? Helpful for everyone!

After the seminar there was an informal chat-session, useful for post-docs to ask questions in a relaxed environment, helped of course by a beer in our hands!

The IPA wishes everyone a nice Summer and we will see you all for our next social event: a barbecue in September, a perfect occasion to give a warm welcome to new post-docs joining ICAMB as well as for all the current post-docs and final year PhD students to get together for the beginning of a new academic year.

Updates will follow on the website.

IPA Committee

IPA is run by Postdocs, for Postdocs. Get involved!

Links

IPA Facebook page: https://www.facebook.com/groups/462376430446559
Institute for Cellular and Molecular Biosciences: http://www.ncl.ac.uk/camb/
Newcastle University: http://www.ncl.ac.uk/
Nature Journal: http://www.nature.com/nature/index.html
Andrew Jermy’s twitter page: https://twitter.com/jermynation

Leading the Way: Inspiring through science

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by Phil Aldridge

“I normally do not like science, but…”

Leonie, Science Set G2, Year 8, George Stephenson High School

This is the opening comment to one of the feedback statements from the 180+ Year 8 students at George Stephenson High School in Killingworth who participated in Leading the Way last week. Leading the Way was coordinated by Leading Edge in collaboration with ICaMB. Leonie’s comment sums up a very inspirational week a team of 15 early career scientists from the Faculty of Medicine had at her school.

Leading the Way was developed based on feedback I had received from Teachers involved in Leading Edge, who wanted to know if it was possible to develop something to work with their year groups rather than just 6 chosen students. After discussions with our Director Rob Lightowler it was agreed to run a pilot scheme to combine the requests of the Teachers involved in Leading Edge and ICaMB’s drive to explore alternative routes to promote our science to the wider community.

We were very lucky to find a school like George Stephenson High School. The School have been a brilliant partner, willing to work with us to develop a program to allow our young scientists to interact with Year 8 (12-13 years old) during one week of their science lessons. A note to worried supervisors and Institute Director – this may sound a lot but in reality each of us involved in running Leading the Way had 12 direct contact hours.

With the help of the science department, we split the year group into teams of 7-9 students based on their science sets.

Our timetable was as follows:

Day 1: Year 8 off timetable to experience “Science in Action”

Day 2-4: We used the timetabled science lessons (2 per set) to create a poster on the topic chosen for the week. Each group worked with one of our scientist team.

Day 5: There was a poster competition with the winning entry earning a day visiting ICaMB.

Some of the Day 1 high points included the isolation of DNA from strawberries, using the isolation of apple juice to experience enzymes in action and playing with alien blood (milk with blue food colouring – see above).

On Day 5, while their posters were being judged, each team built a tower out of 200 straws and sellotape. The goal was to build the tallest self standing straw tower capable of holding a 50 ml Falcon tube containing sweets. We had expected them to require some guidance. However, to everyone’s surprise, Teachers and Scientists alike, all offers of help were refused as the entire year group wanted to do this task alone.

Then the prize giving. We came up with a series of competitions: Best Team Name, Most Visual Experiment, Most Accurate Experiment, Most Volume of Juice isolated, Largest Tower, Best Poster Design and the Big one: Best Idea.

Accuracy and volume were decided on a bar chart and standard curve the teams were asked to produce. This was based on one meeting had with the Science department who suggested we explore data analysis with the students in some way.

Our Judges were ICaMBs own Dave Bolam, Kevin Waldron, Paula Salgado and GSHS Head Ian Wilkinson.

A highlight for the entire Leading the Way team was experiencing the enthusiasm for science from students of all abilities. The winning team who will be visiting ICaMB was Au from Set S1 with their very artistic poster on Mad Cow Disease.

A big thank you goes out to:

– the Leading the Way team: From ICaMB Kayleigh Smith, Simon Syvertsson, Lauren Drage, Martin Sim, Mark Turner, Sarah Billington, Lorna Young, Nichola Conlon & Pippa Harvey and from ICM, IAH, NICR and ION: Elizabeth Gemmel, Laura Mottram, Emma Woodward, Karen Fisher, Joseph Willet, Sanjay Vijay

– the George Stephenson High School Science Department:  lead by Andy Williams and our Liasons Dr James Henderson and Rachel Grimmer.

– the ICaMB supervisors: for allowing the ICaMB LTW team members for being part in this truly inspirational pilot: Mike Gray, David Thwaites, Colin Brown, Caroline Austin, Phil Aldridge, Leendert Hamoen, Brendan Kenny and Jeremy Brown.

Watch this space – we aim to have a second blog post in a few weeks describing their visit….