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Swine Flu: My PhD Story

Aug 13 2009 18:36
Jessica Bland
Deena Blumenkrantz is a PhD student looking at how animal flu viruses are spread amongst humans. She spoke to us about how swine flu has affected her work.
Sourcing Flu in the Lab!
Flu Virus

Drawing a diagram of the flu virus, Deena patiently explains again. The knobbly bits on the outside of the circle are the proteins on the surface of the virus. The eight lines in the middle of the circle are gene segments inside the virus or, more properly, strands of genomic RNA. The surface proteins are encoded by the genes which, in flu, are highly variable.

Ok, so what is it about these viruses you are interesting in?

"When a flu variant crosses the species barrier, say from pig to human, it doesn't necessarily have the ability to spread amongst humans until it has a way of escaping the cell it is made in. I am trying to understand the mutations that occur in order for this change to happen."

"I am interested in one of the proteins called Neuraminidase, NA for short. This protein is known to help the virus cut itself free from the cell in which it grew. By releasing the binding protein, HA, from the cell surface, it helps the flu virion escape its host. NA is also the target of the drug Tamiflu."

"My hypothesis is that changes in NA lead to human-to-human transmission of a virus that previously could only spread from an animal to a human or an animal to animal."

Does that mean that without changes in one of the knobbly bits on the outside of the recent swine flu variant, it wouldn't have spread between humans in the US or Mexico in the first place?

"That is part of what I am investigating. One of the unique aspects of the recent havoc-inducing swine-origin strain is that the closest genetically - related ancestors to the NA protein were all isolated from pigs in Eurasia. While the other seven genes are of North American origin."

"Before this new swine-originated variant was known I was already looking at incidences of avian flu. While H5N1 (the recent avian variant) has infected many humans, it has not acquired the ability to transmit between them."

How does that work fit in with what other researchers at Imperial are doing?

"At Imperial, I am part of a team looking into the many aspects that aid transmission of flu viruses. The other half of my lab group looks at how pathogenic, or dangerous, flu viruses are. In the same way flu mutates to become more transmissible, it can also mutate to become more damaging to its host."

"Flu's replication machinery is not known for its fidelity, in fact, it makes a ?mistake' about every 100,000 bases. That means that each new genome generated has about one to five differences. This is how it evolves. We are trying to understand how little changes affect the spread and pathogenicity of flu."

What was it like in your department when the swine flu news first broke?

"Someone sent an email round on the Saturday night about the spread of a new flu virus in Mexico. Then emails started going back and forth about whether or not it had been sequenced ? we wanted to know if anyone had yet analysed the RNA sequences of the virus."

"The first sequence came from a boy in California and called California/04. We wanted to find out whether there was anything new in California/04 that related to the specific genetic sequences we know about from previous pandemics."

It's like I won the lottery, except I still had to go to work - in fact, my workload had just doubled.
Deena Blumenkrantz

"At Imperial, our first priority was looking for signs of pathogenicity. In particular, Manuela Mura, the post doc in our group who studies the polymerase, a component of flu that drives replication, looked for a mutation, associated with increased activity of avian-like strains in humans. Meaning that if this mutation was present, we would be in trouble. Luckily, it was not and we were able to pass on this information to my boss, Professor Wendy Barclay, who in turn shared it with the public later that day on TV."

How did the pandemic affect how you work?

"Early on, activity in the lab was manic. I felt like I had won the lottery, except I still had to go to work ? in fact, my workload had just doubled."

"Within the first weeks, after it became obvious that this strain was going to last, a group from upstairs approached us, saying they were good at a certain technique that might be useful. The technique, called Pyrosequencing, quickly sequences a short fragment of a gene and can tell you if a mutation has occurred. This is particularly important for the NA

gene, because one nucleotide change can render the NA protein drug resistant! We were able to provide them with sequences and controls so that they could develop the assay so it is ready if the hospital here wants to call on them to identify people infected with strains insensitive to Tamiflu.

The result of this few-hour-test could inform a doctor that they should treat a patient with Relenza, the other anti-viral, instead of Tamiflu."

"But in scientific research you must be patient and thorough and believe that your systematic gathering of knowledge will someday be important. About a month after the outbreak, I now realise that the research I plan to pursue, inspired by this pandemic, will be most relevant to efforts to thwart future pandemics."

During this period, did you have any contact with the media? What kind of things did you have to do?

"Initially, we were on the internet gathering information and feeding it to Wendy so that she could provide the media with informed answers to their pressing questions. The only work that was pushed ahead was the design of our very own tailor made replicate of the swine-origin flu strain."

"There were some really funny bits. When CBeebies, from BBC kids TV, came to our lab we had to do unusual things for the camera like pipetting the pink liquid we usually use to decontaminate our plastic wear. It was entertaining to see them running around our lab like it was a playground."

"We also answered questions for the "Round Up" sent out by Imperial College's Press Office. We were able to offer information about things like why the world was previously concentrating on avian flu and less notice was given to swine flu; between 2005, when avian flu first emerged, and 2009, 257 people out of 421 infected with avian flu had died. Meanwhile, over the same time period, only 11 people in the US were documented to become infected with swine flu and they all recovered."

Has the experience put you off working in a field that can change so suddenly, and which can get so much press attention?

"No, not at all."

"I moved into infectious diseases from cell signalling because I wanted to be involved in something that helps people; I wanted to be involved in creating vaccines. I'm not working directly on vaccine creation now, but we talk a lot about how they should be made better."

"I hope I can keep working in this area, when I finish my PhD. If not in transmission or flu specifically, then definitely in work related to infectious diseases. And throughout my career, I hope that I can bring clarity to public understanding of science through the media."

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