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Dr Jacqueline Smith on the genetics of birds

Birds as models for human disease, the genetics of resistance, a paper accepted right away and her dream of being a famous Egyptologist.

Dr Jacqueline Smith in the lab at The Roslin Institute.
Dr Jacqueline Smith in the lab at The Roslin Institute.

Dr Jacqueline Smith is a genome scientist at The Roslin Institute. In this interview, she talks with Science Communication student Alex Bradie about all the exciting genomic work she is doing in birds. She specifically looks at avian flu as well as birds in tropical countries with a view to helping backyard farmers.

Could you describe your work in a nutshell?

I work in the field of avian genomics and there are three threads to my work. The first is to improve and develop current and novel bird genomes.

The second one, which is the main part of my work, is using the genome to look at the host response to avian viral infections. The main viruses I look at are Marek's Disease and Avian Flu. The overall aim is to hopefully identify genes that are responsible for disease resistance in birds.

The third part of my work is with the Centre for Tropical Livestock Genetics and Health (CTLGH). We are sequencing the genomes of hundreds of indigenous birds from Ethiopia, Nigeria and Tanzania with a goal to improving their productivity. We also want to find out why they are more resilient than birds in the UK and why they can withstand temperature extremes.

How did you become interested in this field of research?

When I first started and decided to go to university, it was actually chemistry I was interested in. But when I started my degree, I realized that chemistry wasn't really for me and it was the biological side of things I was interested in. So I ended up obtaining a biochemistry degree, after which I studied for a PhD in fungal genetics.

I realized I was interested in genetics at that point and upon finishing my PhD, a job at Roslin came up which was concerned with mapping genes to chicken chromosomes. I've worked on chickens and various other birds ever since!

Why is avian genomics research so important?

It's really interesting because mice have generally been the model organism with which to study human health and disease. But, by studying birds and their genetics, we've learnt that they are a really good model species to work on.

Birds are actually very good for doing comparative genetics with humans and they are well placed in the evolutionary tree for doing comparative evolutionary work. Chickens have also proved to be an excellent developmental model for a long time.

When I started my research, I was just mapping individual genes one at a time. Now, technologies have moved on at an incredible pace and we can produce whole genomes in no time at all, and at very little cost. The amount of information we can get from the whole genome is immense. It is also perhaps easier to justify and to obtain samples from birds than from humans!

With regards to investigating disease genetics in birds, it is of particular importance at a time when we need to secure our food source and safeguard the poultry industry as the world population expands and zoonotic diseases pose an increasing threat.

Why are birds better models than mice?

Obviously mice are very easy to work with in the lab, given their short generation time, so I think that's why people have generally studied them. But when you look in birds at the genetic level, the actual conservation of gene order is much more comparable to humans. There is less genomic 'scrambling' across the chromosomes and the genes are more aligned with the human genes, so it’s easier to compare those species. So, certainly from a genomics point of view, chicken is a great species to work with.

Are you working on specific projects?

The main projects I'm working on are concerned with avian flu and that's my main priority. We've got two projects on at the moment, one is looking at different bird species and how they respond to different flu infections ‒ whether that is a low pathogenic virus or the highly pathogenic variety.

Some of the birds we are looking at are very susceptible to disease and others are highly resistant. It's really interesting to see what genes the resistant birds have that the susceptible birds don't and what mutations there may be in the genome that are conferring resistance.

We also have another project, purely with chickens, which are normally very susceptible to avian flu. We're looking at chickens which were able to survive a natural outbreak of highly pathogenic flu. We are studying these birds and trying to find what is making these particular chickens resistant. It's quite a novel thing that we haven’t had the opportunity to study before.

How do you see the future of your research?

We are really just at the beginning with regards to the flu work. Very little is really known about the genetics behind resistance in birds, so it's quite exciting to be involved at this stage and hopefully be able to identify the genes that are involved in resistance.

The next stage would be to functionally test our candidate genes to see what effect they're having ‒ are these particular genes blocking entry of the virus into the bird or are they somehow managing to kill the virus before it can replicate too much?

The important thing would be to be able to stop the birds from shedding virus, so it doesn't spread. Again, everything we learn in birds has wider implications because of the potential threat to humans. It's a very exciting time to be doing this kind of work.

Can you tell me about a challenge that you've experienced during your research?

I think science can be a challenging profession due to the nature of the work. It's a very insecure type of job as, until you get higher up the career ladder, most of the contracts are short term, so you are continually changing jobs or looking for funding to stay in the same job.

Funding itself is very competitive and can be very difficult to obtain. So I don't really have the time to do a lot of the actual research myself, most of my time is spent writing papers and developing funding grants.

I think the nature of my work is also very challenging as it involves a lot of computer analysis and large data sets. So, actually finding computing resources to handle these vast quantities of data and even finding the staff can be tricky. Finding a really good bioinformatician who can do all the correct analysis but also has that biological background is sometimes difficult – anyone who can do both the computing and experimental side of things is like gold dust!

Do you have a favorite project from your time here?

It's very difficult to pick just one. Every project is interesting and exciting in its own way. As I've said, I'm really enjoying all the flu work at the moment; it's a good time to be studying avian flu.

I do remember one of the very first pieces of work I did. The chicken was just being developed as a model for genetics and genomics work. I was looking at individual chromosomes under the microscope and these had been labelled with fluorescent dyes. I was really just laying down some fundamental research to see how much DNA there was in the genome, determine the size of the chromosomes, the length of the chromosome arms, etc.  in order to define the genetic parameters of the genome.

And so after completing what was really a  straight-forward piece of work,  I remember writing my first paper and defining all these genome parameters. To my surprise, it was accepted straight away, with absolutely no corrections and I thought 'this is really easy!’' I soon learned this was not normally the case! Even so, I was pretty chuffed with that.

Can you tell me about a real world application of your work?

The obvious outcomes from my work are with avian flu – whether that be with developing resistant poultry or helping improve vaccine design. However, there are also other diseases that affect chickens, such as Marek's Disease. This is caused by a herpes virus that infects chickens and although it doesn't infect humans, it acts as a good model for human lymphomas because it's a cancerous virus. Studying how it reacts in the chicken, and what effects it has on the bird, has implications for human health.

Another project that has potential applications is the work we're doing with the tropical birds. We find there is lots of genetic novelty in these birds and that their genomes are really quite different from that of the commercial birds that we have in the UK.

By looking at the genetics of those birds we may find ways of improving productivity for the small backyard farmer in poorer countries, with potential benefits to the economies of developing countries.

Why do you think tropical birds have such different genetics to the ones over here?

Birds in tropical countries are out in the wild and are not kept in production facilities as we have here. Commercial bird lines are bred over and over again and are maintained for specific traits such as high growth or laying more eggs. In this way, other traits are often lost.

These birds that are out in the wild are exposed to extreme temperatures, disease, and so many different things. So through evolution and their genetics, they have become really robust and can often withstand much more extreme environments than birds from large industrial premises.

And finally, if you weren't a scientist, what would you be?

It still has a kind of scientific basis, but I've always been fascinated by Egypt and I love history so I've always fancied being an archeologist. In my head I can see myself being this famous Egyptologist, but I know reality would probably involve digging in a muddy field somewhere in the UK!

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