AcademiaNet: Dr Rising, you have chosen a very interesting area of research: spiders and spider silk. Could you maybe summarise what exactly you are working on?
Dr Anna Rising: In my lab, we make artificial spider silk. Natural spider silk actually is the toughest fibre known to man, and it is a very interesting material for medical applications. But any large-scale production of the silk using spiders is not possible: spiders are cannibalistic and they only eat live prey, so it is really tedious to rear them.
Therefore, we produce spider silk in another way: We take the spider silk gene from the spiders and put it into another organism that is more easily handled – bacteria, for example. And then we make the bacteria produce the silk proteins for us. Of course, people have done this before, but it has been problematic because the silk proteins clump together in the bacteria.
What we have succeeded in for the first time is mimicking the spider silk formation process. So we make artificial spider silk by letting bacteria produce the spider silk protein in a soluble form. Then we spin the proteins the fibre, using the same conditions in which they are formed in a spider. This is very different from alternative harsh, chemical approaches, which actually destroy the structure of the silk protein – with those techniques you end up with something that looks like a fibre, but that material is very different from the well organised, natural spider silk.
What are you using these artificial fibres for?
We are studying if we can use these fibres for healing spinal cord injuries or for lab applications – for example using them as a matrix for culturing cells in a 3D-environment. That is one of our focuses right now.
But we also pursue another line of research: we try to develop new lung surfactant preparations inspired by spider silk proteins, and adapt them for drug delivery in the lung. This stems from our insight into how spiders manage to keep aggregation-prone silk proteins at high concentrations in their silk glands before they spin them into a fibre. The silk protein looks like a long string with a ball in each end. We discovered that the first ball is responsible for keeping this sticky protein in solution at high concentrations in the glands before being spun into fibres. So, we thought, maybe we can use the first ball – and not the rest of the protein – and fuse it to other medically interesting proteins, and enable their production in bacteria. That actually worked! We could produce lung surfactant by using this method in a very efficient way.
So to make these lung surfactants you take advantage of some of the properties of spider silk proteins?
Exactly. This was a rather unexpected finding – one that we stumbled across, and we then realised we could produce drug candidates using this method. It's a kind of biomimetic: we learned how the spider manages keep their silk proteins in solution and then we applied the method to some other proteins that are also very aggregation-prone.
I have a confession to make: I am actually an arachnophobe. I am really scared of spiders, so I was wondering: How did you come to study spiders? Were you always intrigued by them?
Well, I don't think I have ever been afraid of spiders, but the more I learn about these fantastic creatures, the more fascinating they become and the less scared I get. So, when I talk about spiders with others, after a while they come to realise that too and say "I killed spiders when I saw them, but now I don't do that anymore because they are quite remarkable".
I don't know how I ended up studying spiders specifically – it was kind of by chance, I think. I am a veterinarian by training, and when I finished vet school I wanted to do some research. Then I stumbled across a PhD opening that focused on making artificial spider silk – that was in 2003. So, first thing I did was going to South Africa and catching spiders there!
Are you still working with spiders from South Africa?
In my labs, we use a few different spider species. One is from South Africa, and it is called Euprosthenops australis. Then we have a Golden Orb Weaver, Nephila clavipes – they were actually caught in Florida. And then we also use a species of Chinese garden spider.
We use those different spiders because we realised that their silk proteins have different properties. So we mix the best or most suitable parts of the proteins from different spider species. The protein we produce now is actually a chimera –a mix from two different spider silk proteins.
Do you keep any live spiders in your lab to harvest the natural silk and compare it to your artificial one?
We do have spiders in the lab every now and then. But it is quite difficult to keep them, especially during winters. You have to provide them with food – live food. Growing flies and crickets isn't exactly popular in the lab… So right now, we don't have any. But as a reference material we do use the natural silk, yes.
Are the spiders you sometimes host those huge, orb weaving spiders?
They are all pretty big, and the ones from Florida make those beautiful orb webs. The South African ones make a different web – a funnel web. It looks like a sheet that narrows down into a funnel, which is built into a hole in a ground. So when the spider's prey ends up in the web, the spider sitting in the funnel feels the vibration – then it latches out and catches the prey. It's a different hunting strategy to that of the orb weaver.
The nets of funnel-web and orb-weaving-spiders probably have very different properties. Could you potentially use them for different medical applications?
I don't think anyone really knows yet. The orb-weaver alone, for example, can spin up to seven different kinds of silk. Personally, I think we can learn a lot from different silks: they have different mechanical properties, and likely also different properties when they are implanted or used medically.
You mentioned some potential applications of the artificial spider silk, like the treatment of spinal cord injuries. Are you still working on tweaking your chimeric fibres?
Yes – we are actually trying to make even stronger fibres! The ones we make right now are reasonably strong – they have about the same properties as mammalian tendons. To make them stronger, we are working on improving our spinning apparatus and we are also looking at making changes to the artificial spider silk protein to increase the binding strength between the molecules in the fibres.
Spinning artificial spider silk | This graph from Dr Rising's paper, published in Nature Cell Biology, depicts the generation of her novel artifical spider silk. Image courtesy of Dr Anna Rising.
You have also co-founded a start-up company – Spiber Technologies – to bring your artificial spider silk to the market. What did you find particularly exciting or challenging about this endeavour?
I think it was a lot of fun, actually. After my dissertation, we had this patent that we wanted to continue using. To do that, we needed to find some money to support the patent application and create the company. I was very lucky that I had worked with a professor – Jan Johansson – who had some connections to investors. He contacted them and they were willing to invest in our idea and we started this company together. We have collaborated ever since.
For the first five years, I was also the CEO of Spiber. I then realised that we needed a lot more research to take this further. When I was offered positions at two different Universities - one at the Karolinska Institutet and one at the Swedish University of Agricultural Sciences– I decided to go in that direction rather than staying on the business side.
When you started Spiber, did your University help you with the patent application?
In the beginning we had some EU-funding, and part of the budget was for IP issues – so we could protect this idea ourselves. Afterwards we of course had to find more funds to keep the patent application going. At that time it was not easy to find financing for this from Universities. Plus, in Sweden, if you are employed by a University, you actually own your inventions – so Universities don't have much to do with these patents. Sweden is an exception in that regard. In most other countries the University owns part of the patent. In that way, here in Sweden, you are actually free to pursue your own ideas. Creating a start-up takes lots of time and energy, and committing to that is much easier when you own your invention.
Right now you are leading two lab groups in two Universities, which are situated in two cities. That sounds very stressful!
It can be. But it has its advantages as well: You get a large research network and you can take advantage of different equipment and know-how at the two Universities. It has been really good for me and my research.
So you founded your own company, you have two lab groups and you can already look back on a very successful career. What is your secret?
I fear I don't have one. Unfortunately I didn't find some kind of magic solution on how to build a successful career and how to balance my work and private life. But I think I have been very lucky to meet and work with the right people: I have had a lot of very competent co-workers that have helped me, and I have met people who have become mentors to me. I feel that was very important!
I also think I am fortunate to have chosen a subject that everyone can relate to. You can talk about it at a party because people find it interesting and exciting.
You mentioned your private life: You have also started a family, and you have two children. Do they like spiders?
They do, actually! I think they have been trained to respect them since they were very small.
At AcademiaNet, we want to highlight successful women in science. It is possible that a budding female researcher is reading this article right now, and she may be wondering how she could get to where you are. Have you got any words of advice for her?
Well, I think – in general – young women tend to worry too much about how to become a scientist and how to choose what they want to research. I would recommend them to get a solid education, work hard and try to get hands-on experience in different research areas. You don't always immediately know what will be your calling, and this way you can try out different things and find out what you like – while building a valuable network. Being a scientist is a fantastic way of working, because your work is actually like a hobby. Plus, basically you are free to do whatever you like, and you can set your own schedule. Last but not least, having a research career and children definitely is possible!
Thank you very much for the interview, Dr Rising!
AcademiaNet welcomes its 2500th member: Dr Anna Rising
Questions were asked by Michaela Maya-Mrschtik for AcademiaNet.