Monthly Archives: February 2015

PhD studentships for 2015 – now recruiting!

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As final year undergraduate students up and down the country approach the end of their degrees, it’s decision time. For many, postgraduate studies are the chosen route in the topic that has excited them the most during the their undergraduate studies. If you, or a friend/colleague, are one of those that find Cell and Molecular Biosciences the main topic of interest, this post is for you.

A view of Newcastle, taken during ICaMB's annual boat trip - you could join us next year!

A view of Newcastle, taken during ICaMB’s annual boat trip – you could join us next year!

Would you like to do your PhD in one of the top UK Research Institute for Biological Sciences?  In a city that has just been voted as the best city in the UK? Then one of the PhD studentships currently available at ICaMB could be what you are looking for!

As an ICaMB PhD student, you will benefit from being in a dynamic and well funded research environment with access to state of the art technology.  You would be working amongst leading experts in several fields from bacterial cell biology all the way through to eukaryotic cell signalling and cancer research.

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We all know that a PhD is not only about your research, so you will also be part of a thriving community of postgraduate students, with many events, both social, scientific and career oriented, organised by ICaMB’s PhD student association PAN!C.  You can read more about PAN!C in a previous ICaMB blogpost.

Here we list MRes/PhD Studentships scheduled to begin in ICaMB in September 2015.  These are also listed on the ICaMB website, where you can also find further details and guidelines on how to apply.  However, if you would like further details about the projects, you can contact the named supervisor directly or the ICaMB Postgraduate Tutor Dr Tim Cheek (email tim.cheek@ncl.ac.uk). In addition, the Institute expects to kick start the careers of several new academic recruits by offering associated postgraduate studentships in the new academic year, September/October 2015. These posts will be advertised before the end of February 2015. If you are potentially interested or would like more details at this stage, please contact Professor Bob Lightowlers, Director of ICaMB. (Robert.lightowlers@ncl.ac.uk)

Newly added:
Title: Investigating the nanoscale structure and function of the bacterial cell division machinery
Sponsor: Newcastle University
Supervisor(s): Dr Seamus Holden, Prof. Jeff Errington
Contact for further details: Dr Seamus Holden (seamus.holden@epfl.ch)
Interested in combining bacterial cell biology with cutting-edge super-resolution microscopy techniques to figure out how bacteria divide?
The structure and dynamics of the bacterial cell division machinery remain mysterious, because this machinery is spatially organized on the nanometre scale, below the resolution of conventional light microscopy. The studentship will focus on using single molecule super-resolution microscopy to study bacterial cell division in living cells, in order to elucidate the physical mechanisms of cytokinesis. Cross-disciplinary training will be provided in advanced microscopy, biophysics, molecular biology and microbiology.
Deadline: This position will be advertised shortly. In the meantime, please contact Dr Seamus Holden for further information.

 

8Pathogens

Title: MRes/PhD Studentship in the Institute for Cell and Molecular Biosciences – Ebola Virus Vaccine: Development of a Salmonella-Based Vaccine Delivery Platform – Ref CB113
Sponsor: Barbour Foundation
Supervisor(s): Dr Anjam Khan (Newcastle), Dr Pietro Mastroeni (Cambridge University) and Dr Gary Kobinger (Manitoba University, Canada)
Contact for further details: Dr Anjam Khan
Interested in contributing towards the development of a novel Ebola virus vaccine?  Ebola is a highly virulent virus causing severe haemorrhagic fever with a high fatality rate in humans. This PhD project will explore the application of Salmonella as a novel oral vaccine delivery system for Ebola.  The studentship will involve designing and constructing new vectors to optimize the expression and immunogenicity of recombinant Ebola antigens.
Cross-disciplinary training will be provided in molecular biology, microbiology, biotechnology, infection, and immunity.  Training will also be provided in the collaborators laboratories in Cambridge.
Further Information

Title: STFC Funded PhD Studentship in Biophysical Chemistry – Creating realistic models of bacterial outer membranes for antimicrobial research and diagnostic assay development – Ref CB114
Sponsor: Science Technology and Facilities Council (STFC) & OJ-Bio Ltd
Supervisor(s): Prof Jeremy Lakey, Dr L Clifton & Dr V Lawson
Contact for further details: Prof J Lakey
This studentship builds up on recent successes in the Lakey research group developing accurate models of the outer membrane of Gram negative bacteria. These will enable more efficient research in antimicrobials and diagnostics. The successful applicant will demonstrate enthusiasm for this cross disciplinary area of research and any science degree including biochemistry, chemistry, physics etc. is suitable. The project involves a collaboration between Newcastle University, the Rutherford Appleton laboratory and OJ Bio, a young diagnostics company. The student will spend time at the neutron source at the Rutherford Appleton laboratory at Harwell.
Further Information
Deadline: The position will remain available until suitable candidates are appointed. Early application is advised.

Title: Sporulation in the human pathogen Clostridium difficile: structural and functional studies – Ref CB115
Sponsor: Medical Research Council (MRC)
Supervisor(s): Dr Paula Salgado and Prof Waldemar Vollmer
Contact for further details: Dr P Salgado
Are you a keen, motivated student, with an interest in microbiology and/or structural biology and an inquisitive, curious approach to research? Interested in bacterial pathogens, antibiotic resistance and in bacteria causing hospital acquired infections? The student will benefit from exceptional training in diverse disciplines: molecular and cell biology, protein purification, structure determination and PG biology to provide new understanding into Cdiff sporulation that would open new therapeutic avenues.
Further Information
Deadline: The position will remain available until suitable candidates are appointed. Early application is advised.

 

Eukaryotic cell biology and ageing

Title: The impact of a senescent-like phenotype in post-mitotic cells and its impact on ageing – Ref CB116
Sponsor: Medical Research Council (MRC)
Supervisor(s): Dr J Passos, Prof D Young & Dr N LeBrasseur
Contact for further details: Dr J Passos
This project aims to understand mechanisms of ageing using mice models, particularly the role of telomeres and mitochondria  and inflammation in the process. It involves a rotation in the Robert and Arlene Kogod Center on Aging, Mayo Clinic (US).
Further Information
Deadline: 28th February

Title: Role of mitochondrial Reactive Oxygen Species in Parkinson’s disease – Ref CB117
Sponsor: Medical Research Council (MRC)
Supervisor(s): Dr A Sanz, Dr A Reeve, Dr V Korolchuk & Prof D Turnbull
Contact for further details: Dr Alberto Sanz
The project aims to better understand the causes of Parkinson’s disease creating new Drosophila melanogaster models and using mammalian cell cultures.

Further Information 
Deadline: The positions will remain available until suitable candidates are appointed.  Early application is advised.

 

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One new aspect of the PhD studentships on offers this year is a renewed partnership with the Universities of Durham and Liverpool, with which we have a joint BBSRC Doctoral Training Partnership. This is a strategic partnership in Biosciences doctoral training between three research-intensive universities in these three northern cities of great industrial heritage.

The Partnership is offering up to 16 four-year fully funded studentships starting in October 2015. A wide range of 28 projects across the Partnership are available for application under the broad themes of Agriculture & Food Security, Bioscience for Health and World Class Bioscience.

As the leading institute in Newcastle carrying out BBSRC-funded research, many of the projects on offer in Newcastle will be based in ICaMB.  Please note that these research projects are in competition for funding with one another. There are two stages to the selection process and usually the projects which receive the best applicants will be awarded the funding.

Projects available at ICaMB, deadline 28th February

Title: Investigating the essential role of copper in biotechnologically important bacteria
Sponsor: BBSRC DTP
Supervisor(s): Prof C Dennison, Prof J C Murrell & Dr K Waldron
Contact for further details: Prof C Dennison
Further Information

Title: Communication across the membrane during bacterial cell division
Sponsor: BBSRC DTP
Supervisor(s): Prof R Lewis & Prof W Vollmer
Contact for further details: Prof R Lewis
Further Information

Title: Role of telomere-driven senescence in age-dependent muscle decline
Sponsor: BBSRC DTP
Supervisor(s): Dr J Passos, Dr Aphrodite Vasilaki & Dr Nathan LeBrasseur
Contact for further details: Dr J Passos
Further Information

Title: Interventions that affect fitness of cells and animals with dysfunctional telomeres
Sponsor: BBSRC DTP
Supervisor(s): Prof D Lydall, Dr N Kenneth, Prof A Morgan & Prof C Price
Contact for further details: Prof D Lydall
Further Information

Title: Fungal-specific RNA endonucleases: novel targets for anti-fungal agents
Sponsor: BBSRC DTP
Supervisor(s): Dr C Schneider, Prof M Caddick & Prof J Quinn
Contact for further details: Dr C Schneider
Further Information

Title: The impact of novel chromatin regulators on genome stability
Sponsor: BBSRC DTP
Supervisor(s): Dr L Maringele & Dr S Grellscheid
Contact for further details: Dr L Maringele
Further Information

Title: The identification of key virulence factors involved in the host-bacterial interaction of Salmonella typhimurium ST313
Sponsor: BBSRC DTP
Supervisor(s): Dr P Aldridge & Prof J Hinton
Contact for further details: Prof P Aldridge
Further Information

Title: Virulence factors of human and bird Trichomonad parasites targeting host proteoglycans: integrating evolutionary biology, comparative genomics, biochemistry and cell biology
Sponsor: BBSRC DTP
Supervisor(s): Prof R Hirt, Dr D Bolam & Prof N Hall
Contact for further details: Prof R Hirt
Further Information


Title: Re-engineering the metabolism of the bacterium Bacillus subtilis for the synthesis Mycosporine-like amino acids
Sponsor: BBSRC DTP
Supervisor(s): Professor C Harwood (Newcastle), Dr Malcolm Horsburgh (Liverpool), Dr Douglas Cossar (Croda Europe)
Contact for further details: Professor C Harwood
Further Information

Title: Ammonium sensing in the wheat pathogen Zymoseptoria tritici
Sponsor: BBSRC DTP
Supervisor(s): Dr J Rutherford, Prof B van den Berg and Dr A Sadanandom
Contact for further details: Dr J Rutherford
Further Information

 

Donating hope – a success for parents in danger of transmitting mitochondrial disease

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 by Prof Bob Lightowlers

It was 2pm on a Tuesday afternoon and there I was watching television in my office. An unusual experience (honestly) but it was to be a truly momentous occasion. For the next 90 minutes, members of parliament would be debating whether to sanction the procedure of mitochondrial donation. What on earth does that mean ? Well, mitochondria are essential compartments (or organelles) that provide numerous key functions for the cell. They also have their own genome, called mitochondrial DNA – mtDNA – that contains the information to make up just 13 proteins, all of which are important in their function of producing main energy source of the cell, ATP. This is why mitochondria are often referred to as the cell’s batteries or the powerhouse of the cell. It is important to note that mtDNA is very small when compared to the nuclear DNA component: 16 thousand mitochondrial nucleotides (that is, the “letters” in the genetic code) vs more than 3 billion nucleotides in the nuclear DNA.

OK, but why would you want to donate mitochondria?

Mitochondrial DNA is strictly passed down via our mothers, unlike nuclear DNA which is comes from our father and mother. Almost 2,500 women in the UK have mutations in some or all of their mtDNA that can cause disease. Defects of this mitochondrial genome, can be responsible for a wide spectrum of mainly muscle and neurodegenerative disorders for which there is no treatment. By identifying those women with defective mtDNA, we could potentially prevent transmission of their unhealthy DNA by substituting their mitochondria for organelles from a donor. Simple on paper!

What’s the problem?

There are two major barriers. First, how safe would any technique be for mitochondrial donation ?

The pronuclear transfer method: Embryos are shown with mitochondria carrying normal (green) or mutant (red) mtDNA. As the embryos begin to develop, pronuclei become visible. Pronuclei from the normal donor embryo are removed (blue, top panel ‘enucleation’) and are replaced with the nuclear DNA from the patients (red, karyoplast). The resultant embryo carries nuclear DNA from the patients and mtDNA from the donor (mitochondrial donor zygote).

The pronuclear transfer method: Embryos are shown with mitochondria carrying normal (green) or mutant (red) mtDNA.
As the embryos begin to develop, pronuclei become visible. Pronuclei from the normal donor embryo are removed (blue, top panel ‘enucleation’) and are replaced with the nuclear DNA from the patients (red, karyoplast). The resultant embryo carries nuclear DNA from the patients and mtDNA from the donor (mitochondrial donor zygote).

The technique being championed in Newcastle is that of pronuclear transfer. The idea is to take the nuclear DNA from a fertilised embryo and transfer the DNA to a donor with no nuclear DNA, ie, where the nucleus was removed. The newly made embryo then has nuclear DNA from the mother and father but has only mtDNA from the donor.
As you can tell, there is quite a lot of tricky manipulation here. Further, although the mtDNA that has been replaced carries only a very small number of genes, could these somehow be incompatible with the nuclear DNA?
After many years of very careful analysis, there is no evidence to suggest that this procedure is unsafe. The question of incompatibility would also seem to be highly unlikely. After all, nature has been performing the experiment of mixing and matching nuclear and mtDNA since the evolution of Homo sapiens. The idea that, for example, there would be something wrong with the child of an aboriginal woman and a inuit man due to the substantial differences in their mitochondrial DNA would seem laughable.

In addition, does the replacement of DNA, albeit the complete mitochondrial genome, constitute genetic manipulation? This is a contentious issue and a strict definition of what constitutes genetic manipulation, particularly when concerning mtDNA, is difficult to agree on. It must be remembered that mtDNA is completely separate from nuclear DNA and needs to be considered as such.

A separate issue is that many people are ethically uncomfortable with this process. Can embryo manipulation ever be acceptable? Certainly, many religious people have a deeply felt objection to this.
Even when we accept that these methods could offer such an immeasurable benefit for many couples, it is clear that there were many questions to be tackled before we could consider the prospect of mitochondrial donation. For this reason, experimentation and public consultations had to be initiated.

The Parliamentary Under-Secretary of State for Health, Jane Ellison, when presenting the vote on Tuesday highlighted the measures taken to date to assess the safety and ethical concerns surrounding mitochondrial donation.

The Parliamentary Under-Secretary of State for Health, Jane Ellison, when presenting the vote on Tuesday highlighted the measures taken to date to assess the safety and ethical concerns surrounding mitochondrial donation.

To cut a very long story short, both have been carried out for many years, including supportive public consultations and independent review by the Human Fertilisation and Embryology Authority (HFEA) reporting that the procedure was not dangerous, as we’ve covered before (here and here). Following these procedures, Professors Turnbull, Herbert and numerous members of the Wellcome Trust Centre for Mitochondrial Research were instrumental in persuading the government to finally hold a debate in the House of Commons.

The vote scheduled for Tuesday afternoon would decide whether the HFEA would have the right to offer a licence to perform mitochondrial donation, a first for the UK and the world. The week leading up to the debate was a white-knuckle ride. Letters of support were published in leading newspapers from Nobel Laureates and other eminent scientists. Just when it appeared that the tide was turning, the Church of England announced it could not support mitochondrial donation. This was a great disappointment and rather a shock, as they had been involved throughout the lengthy consultation processes and had not indicated their level of concern.

Now a back-benh MP, former Minister for Science, David Willets, made a clear case in support of mitochondrial donation.

Now a back-bench MP, former Minister for Science, David Willetts, made a clear case in support of mitochondrial donation. You can read the whole debate here.

Back to me watching the television. At 3:45pm, the members had cast their votes and the count was in – 382 for the motion, 128 against! This is a fantastic result. It gives couples who may be at risk of having a baby with mitochondrial disease the chance to choose whether they want to try mitochondrial donation, just like couples have been able to choose in vitro fertilisation since the 1970’s.

Obviously, this result has gathered lots of media interest and even I was rolled out to perform a couple of interviews.

There is still more to be done, however. Further important research to support the safety of the procedure is currently in review but it must be recognised that every clinical procedure carries a risk. What this vote does is to empower the HFEA to licence this procedure in the UK, but this is still an important barrier and many issues are still to be addressed. And it also needs to be discussed by the House of Lords, of course.

Regardless, today’s vote was a wonderful day for anyone who has been touched by mitochondrial disease in any form. Twenty years ago, Doug Turnbull and I used to discuss this idea. He and his colleagues have done a remarkable job to make this pipedream a reality.