Posts Tagged ‘University of Leicester’

Microbiology Anyone?

Sunday, February 14th, 2010

Over on our Facebook page, Heather Collins asked:
Why do so few University's run microbiology degrees these days? And the ones that do insist on merging them with biochem. Do they not realise people just want to poke about with small squiggly things for a career?

And another question – why do so few (UK) universities have microbiology departments these days? There’s been a trend towards bigger academic units, and disciplines who can’t recruit enough students tend to get merged with other departments into units usually called something like “The School of Life Sciences”. In addition, non-human microbiology is out of favour these days, with most of the money going to medical microbiology, and this killed off some microbiology departments who couldn’t or weren’t willing to adapt.

So why do UK universities find it hard to recruit microbiology students? When the A level syllabus changed a few years ago, microbiology all but disappeared. Actually, there is a little bit still there, but not until the A2 stage and it’s no longer offered by all schools. But A2 students have already filled out their UCAS forms. AS students don’t know what microbiology is, so why would they apply to do a degree in it? (They know what genetics is because there’s lots of that at AS level, so many apply to do that as a degree).

Fortunately, there is a solution! At the University of Leicester, we offer you not one but two chances to study microbiology. ”Microbiology” is a broadly based course including environmental microbiology, which “Medical Microbiology” is … well, see if you can figure it out ;-)

Of course, if it’s a bit late for you to be thinking about degree choices, we also offer lots of microbiology PhD and postdoctoral places, so check us out for all your microbiology career requirements :-)

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25 years of DNA fingerprinting

Thursday, September 10th, 2009

Alec Jeffreys Exactly 25 years ago today, Alec Jeffreys, Professor of Genetics at the University of Leicester discovered a technique that has subsequently had an incalculable effect on society, helping to solve criminal cases, resolve immigration arguments and clarify questions of paternity, not to mention creating one of the biggest civil liberties issues of our times. Working in the laboratory, Sir Alec recalls, he and his technician were simply following their noses. They had “absolutely no idea” of the applications that would result from the discovery they stumbled upon.

“I have never approached an experiment with a desire to solve a practical problem,” he observes, pinning down his moment of discovery to precisely 9.05am on Monday 10 September 1984. “My forensic thoughts at 8.55 on that morning were precisely zero; they simply were not there. The technology comes first and then suggests the applications, not the other way around, and you see this over and over again.”

But just as he has spoken out about the ethical and moral issues concerning the use of the technology he made possible, Sir Alec is a staunch defender of Britain’s curiosity-driven research. And the 25th anniversary of his discovery is, he believes, the right time to be discussing its future.

“As scientists, we have to be accountable to the public purse for the money we are spending, but if you take it too far – and in my view it has gone far too far now – it actually stifles the creativity of the very thing you are trying to promote.”

His warning is simple: applied science can be managed from the top down, but we apply the same approach to pure science “at our peril”. “It is blue-skies research that is the ultimate driver – delivering the new techniques, concepts and tools that we need to progress”.

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Study at the University of Leicester

The good news about influenza

Monday, September 7th, 2009

Influenza virus With the fall in H1N1 “swine flu” influenza cases recently, it has become fashionable for the media to run “What was all the fuss about” stories on the same page as “OMG, it’s going to be bad” stories. The problem with influenza is that it is one of the most unpredictable of all viruses, and while an upsurge in the number of cases can be expected as the winter flu season gets going in the northern hemisphere, the real concern is that this new pandemic virus might “turn nasty” in the second wave, just as in 1918 a much more pathogenic variant of that virus followed the relatively benign first wave of cases.

There are two ways in which this could happen. The first is that the present virus acquires spontaneous mutations which make it more pathogenic. The other possibility is that the virus recombines with a highly pathogenic influenza virus though the process known as reassortment – swapping of genes when two different strains infect the same cell. And there’s a good candidate for that out there – the highly pathogenic H5N1 avian influenza virus. Unlike H1N1, H5N1 has a hard time infecting humans, so it’s unlikely that these viruses would meet. But if they did…

The good news comes from Egypt, where H5N1 is relatively common, and a (worrying) case of H5N1/H1N1 co-infection was recently reported. The Ministry of Health has now discounted the rumour of a co-infection with the two viruses. In addition, a University of Maryland/NIH study suggests that co-infections of H1N1 with seasonal flu viruses do not produce chimeric or reassortant viruses. The H1N1 strain seems to outcompete seasonal viruses, possibly demonstrating this pandemic strain is not under biological pressure and is perhaps more efficiently communicable. Certainly, the past pattern seems to suggest that H1N1 pandemic seem to suppress outbreaks of other strains for some time.

A phase I clinical trial conducted by scientists from the University of Leicester tested 100 healthy volunteers with an H1N1 vaccine to see how their immune system responded. Trial leader Dr Iain Stephenson found 80 per cent of the volunteers showed a “strong, potentially protective” response after one dose, with more than 90 per cent showing the same response after two doses. The results suggest that one vaccine dose may be sufficient to protect against A(H1N1) swine flu, rather than two. Larger trials are now under way around the world involving up to more than 6,000 adults and children.

Reasons to be cheeful.

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The Enzyme Club

Friday, July 10th, 2009

Restriction enzyme

“In my day” i.e. when I started my PhD back in 197<cough>, the first few weeks were spent joining the Enzyme Club. This encompassed all the biomedical researchers at the University of Leicester. Each new student would prepare a batch enzyme for recombinant DNA work. In my case, I made Hsu I (an isoschizomer of Hae III but allegedly easier to prepare). Since it was years ago, I can’t remember how many litres of the organism I grew up, but I remember very clearly doing the first assay on two litres of crude extract, and figuring out I was holding £40 million pounds worth of enzyme at the then current market prices. The first affinity column cut it down to £15 million, and a quick gel filtration to couple of millions pounds worth – still pretty good for two weeks work, especially when you remember that two million pounds was enough to buy you a house back in the 1970s!

Why did the Enzyme Club exist? Because these reagents were scarce in the 1970s, and rationed both by price and availability. Only a few years before, the only way to get hold of any of these enzymes was to make your own. This type of open science made sense. Why did the Enzyme Club cease to exist? Gradually, it became clear that the batch of enzyme I made wasn’t very good. It had a persistent exonuclease activity which meant it was fine for restriction analysis but rubbish for cloning, and it went off very quickly in storage, so that after three months there wasn’t much activity left. And although I’ve always been a rubbish protein chemist, that was a pretty common experience. Gradually, the companies dropped their prices and improved both the quality and availability of commercial enzymes. The day came when the Enzyme Club didn’t make sense any more, and it quietly died. It’s probably still moldering in the back of a coldroom over in the MSB.

So boys and girls, this is a story of the economics of open science, which made sense in response to scarce resources. When the availability of enzymes was limiting, this open approach made sense. When time became limiting, we all retreated back into our laboratories and got on with whatever we needed to do to get a PhD. The moral of this story is that open science pops up it’s head when times are hard and resources are scarce, but retreats quickly as the balance changes.

Prions are secreted in milk from clinically-normal scrapie-exposed sheep

Tuesday, June 9th, 2009

PrP All scientific papers are important, but some are more important than others. Aside from its scientific importance, this paper is particularly important to me in purely personal terms. It comes from my own department. Ben Maddison was a PhD student in my laboratory many years ago and now heads up his own research group within the department. It’s also one of the final papers to come from Gary Whitelam, my former head of department, who died tragically last year. And as if all that wasn’t enough, as the UK starts to forget about how close we came to disaster with BSE, we’re still not completely sure that it’s all over.

Using the cutting-edge research technique of serial protein misfolding cyclic amplification (sPMCA), my colleagues show that prions are secreted in the milk from scrapie-exposed sheep. The sPMCA method involves incubating a small amount of abnormal prion with an excess of normal prion protein, so that some conversion takes place. The growing chain of misfolded protein is then blasted with ultrasound, breaking it down into smaller chains and so rapidly increasing the amount of abnormal protein available to cause conversions. By repeating the cycle, the mass of normal protein is rapidly changed into misfolded prion.

Since scrapie is not transmissible to humans, these findings do not indicate the likely introduction of zoonotic prions from sheep into the human food chain. Nevertheless, the data do indicate caution in the risk assessment associated with such foods. Although it is unknown if analogous shedding of prions into milk occurs with bovine BSE, evidence from previous epidemiological and bioassay studies suggests that such a scenario seems unlikely to cause clinical disease. However, the present report strongly suggests that given the importance of cow’s milk in the human diet the potential presence of low levels of prions within milk warrants further investigation. Analyzing milk samples by sPMCA offers a methodology with clear potential for the identification of clinically sick animals and those with preclinical/subclinical prion disease. Such a non-invasive, live animal assay has the potential to contribute to the epidemiological study, management and control of prion diseases within farmed animals.

Prions are secreted in milk from clinically normal scrapie-exposed sheep. J Virol. Jun 3 2009. doi:10.1128/JVI.00051-09
The potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. Here, serial protein misfolding cyclic amplification (sPMCA) allowed the detection of prions in milk from clinically-affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset, irrespective of the immunohistochemical detection of protease-resistant PrP(Sc) within lymphoreticular and CNS tissues. These data indicate the secretion of prions within milk during the early stages of disease progression and a role for milk in prion transmission. Furthermore, the application of sPMCA to milk samples offers a non-invasive methodology to detect scrapie during preclinical/subclinical disease.

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Guardian University Guide 2010 – Biosciences

Wednesday, May 13th, 2009

League table

PhD Research Scholarship: University of Leicester

Tuesday, May 12th, 2009

University of Leicester Applications are invited for a PhD Scholarship commencing in October 2009 to support research on the following project:

A new family of sigma-factor binding proteins; role and mechanism of transcriptional regulation.
Principal Supervisor: Dr Helen O’Hare, Department of Infection, Immunity & Inflammation.

The Scholarship will start on October 1st, 2009, run for three years and provide a waiver of University tuition fees and a student stipend equivalent to that of a UK Research Council award, £13,290 from October, plus an annual £1,000 research training support grant and £300 student conference/travel allowance. Candidates must hold a First or Upper Second Class honours degree (or equivalent) in a relevant discipline. This Scholarship is only available to candidates who are eligible to pay the Home/EU tuition fee, i.e. permanently resident in the UK or another EU country.

Further details about each project are available from the Principal Supervisor. Applications should be submitted as soon as possible by post or online.

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New influenza vaccine research at the University of Leicester

Tuesday, April 28th, 2009

Influenza vaccination New research published yesterday (Monday April 27) from the University of Leicester and University Hospitals of Leicester NHS Trust warns of a six-month time lag before effective vaccines can be manufactured in the event of an influenza pandemic. By that time, the first wave of pandemic flu may be over before people are vaccinated, says Dr Iain Stephenson, Consultant in Infectious Diseases at the Leicester Royal Infirmary and a Clinical Senior Lecturer at the University of Leicester.

Pandemic preparedness plans show that vaccination is critical for controlling pandemics. Some authorities have invested in vaccine stockpiles, but these resources are small in comparison to global demand. The use of stockpiled vaccine is challenged by the need for two doses and secondary manufacturing constraints. MF59, a proprietary adjuvant, was licensed in seasonal influenza vaccines in 1997, and more than 30 million doses have been administered safely so far. These new findings suggest that consideration could be given to advance priming to induce memory responses that enable cross-reactive antibodies to be generated rapidly after infection with the pandemic virus or by a single low-dose vaccination when required at the onset of future pandemic.

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine. PNAS USA April 27, 2009
Proactive priming before the next pandemic could induce immune memory responses to novel influenza antigens. In an open-label study, we analyzed B cell memory and antibody responses of 54 adults who received 2 7.5-μg doses of MF59-adjuvanted A/Vietnam/1194/2004 clade 1 (H5N1) vaccine. Twenty-four subjects had been previously primed with MF59-adjuvanted or plain clade 0-like A/duck/Singapore/1997 (H5N3) vaccine during 1999–2001. The prevaccination frequency of circulating memory B cells reactive to A/Vietnam/1194/2004 was low in both primed and unprimed individuals. However, at day 21 after boosting, MF59-adjuvanted primed subjects displayed a higher frequency of H5N1-specific memory B cells than plain-primed or unprimed subjects. The immune memory was rapidly mobilized by a single vaccine administration and resulted in high titers of neutralizing antibodies to antigenically diverse clade 0, 1, and 2 H5N1 viruses already at day 7. In general, postvaccination antibody titers were significantly higher in primed subjects than in unprimed subjects. Subjects primed with MF59-adjuvanted vaccine responded significantly better than those primed with plain vaccine, most notably in early induction and duration of cross-reacting antibody responses. After 6 months, high titers of cross-reactive antibody remained detectable among MF59-primed subjects. We conclude that distant priming with clade 0-like H5N3 induces a pool of cross-reactive memory B cells that can be boosted rapidly years afterward by a mismatched MF59-adjuvanted vaccine to generate high titers of cross-reactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.

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Guest Post: The Drugs Don’t Work

Friday, April 17th, 2009

Today’s post is from guest blogger Helen Fry, who is a student at the University of Leicester.

MicrobiologyBytes welcomes guest bloggers who would like to contribute occasional posts which conform to the style and content of this site. If you would like to be a guest blogger here, please email your post with a completed copyright release form to me at: alan.cann@gmail.com

Drugs A quick glance at the British National Formulary and it’s easy to see just how many antibiotics are licensed for use in the UK. What is more difficult to see is how many antiviral agents are available, and this is because there are much fewer. The only viral diseases with treatments listed in BNF 57 are HSV, VZV, HIV, RSV, viral hepatitis and influenza. Viruses are the most abundant ‘lifeforms’ on the planet and there is a huge diversity of viruses that cause disease in humans. Viral disease, although often milder than bacterial or eukaryotic disease, accounts for a major burden on the health service and is a considerable cause of morbidity and mortality. Some viral diseases cause very severe infections and are a heavy global issue, such as HIV and viral diarrhoea (a major cause of infant and childhood mortality in countries without safe drinking water). So if viruses are so abundant and are such a global health pest, why are there so few antiviral agents?

There are several reasons why this is the case. First there is the difficulty of researching viral disease. Most pathogenic bacteria can be cultured and investigated fairly easily, with some notable exceptions such as TB and Chlamydia trachomatis. Culturing and investigating viruses is a lot harder, as it requires cell culture methods, where the appropriate line of eukaryotic cells is grown up and infected with the virus. This means that the virus cannot be studied directly, as with a growing population of bacteria, and because they are so small they can only be visualised via electron microscopy (The impact of cell culture sensitivity on rapid viral diagnosis: a historical perspective). There are non-culture based detection methods, but these only confirm the presence of the virus, they do not allow it to be studied. Viruses do not release any compounds on their own, any proteins made are produced in the host cell, whereas bacteria release toxins and chemotactic agents, quorum sensing molecules and siderophores, to name a few. This makes them easier to study. The fact that viruses are harder to study means that less is generally known about them, and it is a lot harder to identify potential targets for antivirals. On the other hand, viruses have much smaller genomes (on the whole, with some obvious exceptions), meaning that the genomes can be sequenced easily (Role of Cell Culture for Virus Detection in the Age of Technology).

Once a virus has been fully characterised, despite the difficulties, it is still problematic to make useful antiviral agents, and even the ones licensed in the UK are often quite toxic. This is for several reasons. Since the most important part of the virus life cycle takes part inside host cells antivirals often have to penetrate the cell in order to be effective. This means that the drug has to be highly specific for virally infected cells or risk being toxic to healthy cells. The viruses use host cell machinery to replicate themselves, meaning that a drug targeted against this part of the cycle risks affecting genome replication in healthy cells unless a virus specific target can be identified. Bacteria are prokaryotes, which mean that their cells are highly different to ours and it is often a simple matter of identifying a difference between our cells and theirs, and finding a molecule that interacts with it, such as the beta-lactams and cell wall synthesis. Antivirals have similar issues to antiprotozoals, in that finding a compound active against the microbe is not that hard, the difficulty lies in finding one that does not interact with host processes and is therefore non-toxic.

Finally, however, it all comes down to money. Drug development is now a process that is left exclusively to pharmaceutical companies due to its prohibitive costs, and since they are primarily a business rather than a service, all activity undertaken by them will inevitably be profit driven, rather than need driven. Bringing a drug to market now costs several million US$ and taken over 10 years from target identification to phase IV clinical trials. It is therefore a huge investment, and the drug companies want to be as such as possible that their drug will make it to market and will make as much money as possible before the patent runs out. Since patents last for 20 years, a drug may only have 5 years to make back the money it took to develop before cheaper generics can be made. This has caused companies to focus on drugs that are least likely to fail trials due to toxicity and that will make the most money in a short amount of time. Therefore the focus has been on lifestyle drugs that people will take every day for years on end, such as statins and antihypertensives, that have a low risk of toxicity and are well established in doctors’ prescribing pads. HIV therapy has benefited from this, as HIV+ people will need to take their medication every day for the rest of their lives. This, along with the fact that HIV is a rapidly fatal disease without medication meaning that drug companies can charge almost what they like for them, has meant that the number of effective, less toxic antiretrovirals is increasing and is already fairly big in comparison to other viral illnesses. Drug companies will risk producing drugs that are more likely to be toxic if they can charge a large amount for them once approved. This is usually the case for life-threatening illnesses, explaining why chemotherapy for cancer costs so much (in the tens of thousands for a single cycle in some cases), but is quite good these days, at least for the common cancers.

The incentive of money can be seen with the influenza drugs. Not many people have the need for influenza antivirals, since there is a pretty good vaccine produced each year for those at risk, and those not in high risk groups do not tend to suffer from severe enough disease to warrant treatment with anything other than blankets and Lemsip. So why are there two good drugs sitting on the market when they are not needed? The answer lies with the government who, fearing an approaching flu pandemic (we are due for one) decided to stockpile the anti-influenza drugs before they were widely used and resistance developed.

The biggest burden of viral disease, as with most infectious diseases, lies in developing countries. They are the worst hit by the HIV pandemic, suffer outbreaks of haemorrhagic fevers, are plagued by water borne viral diarrhoeal diseases and various other viral nasties. However, since they for the most part do not have the capital to fund a national health service and the people cannot afford medications themselves, these countries and their endemic diseases have been largely ignored by the drug companies due to the lack of profit potential. This means that the countries worst affected by HIV are the ones who do not have access to effective antiretroviral therapy, and that children die in the thousands because of viral diarrhoea. Some drug companies are starting to research third world diseases, but progress is slow and funding is not the best. Since we in the west need medications we cannot boycott the companies, and allowing patents to be extended would only put more strain on the already overwrought NHS. However, there needs to be a shift in attitudes towards making the companies more responsible for the drugs they develop.

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