Vicky F
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Viruses; an unlikely tool in the fight against leukaemia in the lab.

Vicky F
Posted by
30 Oct 2013

In this blog post, I’m going to try and give you a bit of insight as to what I’m doing in the lab at the moment, and I’m going to talk mainly about making viruses! No, I haven’t switched careers to become a microbiologist, viruses are vital in researching leukaemia.  As I’ve discussed in a previous post, leukaemia is caused by changes to DNA called DNA mutations.  There are over 25,000 genes (small bits of DNA, which code for proteins) in humans and often only a few of these genes need to be mutated to cause leukaemia.  In the case of the leukaemia I am looking at (one type of acute myeloid leukaemia) the mutation is called a fusion gene, where two genes; AML1 and ETO join together instead of remaining separate.  This stops both of them working properly.  As scientists, we need to find out why this AML1-ETO fusion causes leukaemia, so we can find ways to better treat it and help patients.


There are a number of ways we can use experiments to try to find this out.  If you have had leukaemia, you will probably have been asked if your samples can be used in scientific research. One of the things we do is look at blood and bone marrow samples from patients with this type of leukaemia, but there are a number of difficulties here – one is the fact that once a sample is taken from a patient the cells start to die, despite our efforts to culture them in the lab and keep them alive.  These cells are so used to being in a person, that even if we keep them at body temperature  with all of the growth nutrients they need – the change is far too much for them and they die.  If we want to do an experiment on a patient sample, we have to use the cells straight away. We can look at the DNA to see what mutations there are, or have a look at the proteins on the surface of these cells to see how they differ from normal blood cells.  However, whilst these experiments are very useful, there are some important experiments which we can’t use them for.  For example, if we want to test a new drug on some leukaemia cells, these patient cells are already dying due to being outside of their normal environment, so it’s hard to tell whether the drug is killing the leukaemia cells. 


A way around this is to genetically modify cells which do grow well in the lab – and this is where viruses come in very handy!  Genetic modification is very controversial in things like food, but for scientists it is extremely handy and widely accepted – just last week I genetically modified some bacteria and next week I will be genetically modifying some cells which grow well in the lab called a cell line.  Cell lines are special cells which will continue to replicate forever and every cell within a cell line is the same.  This makes them very useful for experiments in the lab as scientists can grow as many of them as we need.


Viruses cause ailments like the common cold, but also more serious diseases. For example certain types of HPV have been linked to the development of cervical cancer, and HIV which can lead to AIDS if not controlled.  From a scientific point of view, viruses are fascinating, because as opposed to most bacteria, yeasts and other micro-organisms, viruses cannot replicate by themselves.  Viruses have to get their genetic material into cells of other living things to copy their DNA, so they hijack the cell’s DNA copying machinery, using it to replicate themselves many times.  The virus then bursts out of the infected cells to continue its journey and infect other cells.  It’s cheeky, but makes them very good at surviving inside of people and animals.  When the virus infects cells it doesn’t care where its genetic material is inserted, for instance when a virus infects human cells viral genetic material may be inserted into the middle of an important human gene and this can cause the cell to become cancerous.  We don’t currently know for sure how regularly virus are involved in different types of leukaemia and lymphomas, apart from in a few specific cases, such as a type of lymphoma called Burkitt’s Lymphoma (caused by the Epstein-Barr virus), which is thankfully very rare in the UK.  Some cases of Hodgkin's Lymphoma have also been linked to the same virus.  Scientists who study this viral DNA inserted into human cells have speculated that as much as 8% of our DNA may actually originally have come from viruses which has been incorporated into human DNA and carried along through evolution!

So, time to get our own back on the viruses a bit and use them for good.  What I do is take the HIV virus, take out a bit of viral DNA which would allow it to replicate inside human cells (it would be far too dangerous for me to use in the lab otherwise) and then put in the bit of human DNA which I think causes leukaemia (for example AML1-ETO).  I then use this genetically engineered combination of human and viral DNA to produce viruses, which I can infect cell lines with. This is a very important tool for cancer research scientists as it allows us to take a cell line of identical cells and see what happens when we infect some of them with the modified virus which will add the gene which we think is involved in leukaemia (in the case of my research, the AML1-ETO fusion gene).  We can then compare the viral-added gene cells with the normal cells knowing that there is only that one single difference between them – and that any changes in for example, resistance to drugs, or faster cell growth – is likely due to that mutated gene.   It sounds almost magical, but it’s now a pretty routine thing to do – most of the people in my lab that work on leukaemias will be doing/have done this at some point.

While I am interested in what happens when I use virus to add in the AML-ETO fusion gene, I will also put in a bit of DNA which codes for a protein called GFP.  GFP stands for green fluorescent protein, and is a bit of DNA originally from a deep water jellyfish, which scientists chopped out and now use in order to see whether they have successfully infected their cells with virus.  You can see a picture (above right) of one of my cells infected with the virus I made. I know that because it is glowing-green because of the GFP, the cell will also have the AML1-ETO in it. I’m also currently using viruses to investigate handful of other genes which we think are important in leukaemia.  

If you have any questions you think I might be able to answer, or would like to leave some feedback, please do leave them below or a contact me on Twitter – i’ll try my best to respond to everyone as quickly as I can.  I frequently tweet pictures and news from the work im doing in the lab, so if you have Twitter and would like to follow me – I'm @vickyyyf

Thank you very much to @BeckiePort for sharing her expertise on cancer and viruses and for proofreading this article.

HIV viral particle picture is shared under the conditions of the Flickr creative commons licence and credited to user AJ Cann.

Comments

Anonymous
30.10.2013

Very interesting.Also sounds somewhat dangerous for you and the other researchers. Is there any risk?

Anonymous
30.10.2013

Very interesting.Also sounds somewhat dangerous for you and the other researchers. Is there any risk?