In 2012 Anna Falk became an associate professor at Karolinska Institutet in Stockholm. She heads a research team studying molecular mechanisms underlying developmental diseases of the human nervous system. Using iPSC (induced Pluripotent Stem Cell) techniques she models the neural development of a human brain in a dish. Anna has also been tasked with establishing the first iPSCs core facility in Sweden and is in the middle of getting everything up and running.
growing human brains in a dish
We reprogram skin cells from a patient and use the iPS cells and their differentiated progeny as a model to understand the brain development in healthy and diseased. When we compared iPS generated neural cells with neural cells captured from aborted embryos we saw that they are very similar. As a result, we actually do not need cells from the embryo to perform this type of research, which is a breakthrough in itself.
The goal is to look at cells from patients with developmental brain diseases and try to recreate the error in vitro to study wherein the development things went wrong. Our approach allows us to recapitulate human brain development at the cellular level in a dish.
“I want that patient to feel that his/her donation will generate as much new knowledge as possible”
Anna in Aula Medica at Karolinska Institutet, Stockholm, Sweden. Interview June 2014.
Interview with anna:
When did your interest in stem cells and regenerative medicine take form?
Quite early actually! In High school, Natural Sciences and chemistry, as well as biology, really caught my attention. When I found out that there was something combining the fields I was very much intrigued.
Was there someone who inspired or influenced you early on?
My father, he was an engineer. When I was just a small curious girl he gave me these building sets of how to make common things, like an alarm clock. The building sets allowed me to see what was behind the everyday appliance and understand how it worked. There my interest in technology took form.
How about today? Does anyone inspire you?
Heavy hitters during conferences like my former mentors Jonas Frisén (Karolinska Institutet) and Austin Smith (University of Cambridge) inspire me. I get truly excited when they come up with smart simple solutions.
Beautiful science attracts and inspires me, with beautiful I mean that the experiments are performed in a way so that there is no doubt as to the exactness of the result. There are no holes, every angle has been covered. It is impressive to see such experiments where you ask a question or point towards a flaw and then they have already covered it.
What is the main focus of your science today, where do you hope it will take the field in ten years?
The development of a human brain, how does it reach the right size, structure, and organization? These are big questions we hope to answer. Although much of this has been done in mice there are several human developmental diseases that are not present in mice. The mouse brain is different from ours in many ways; they don't have the same amount of cells, they have a different structure and no convoluted cortex. This is why we are trying to mimic brain development in vitro through the use of iPS generated neural stem cells.
It's often discussed that science soon can cure diseases like Alzheimer and Parkinson but when I listen to you, it sounds as if there is still a need for basic research?
That´s true, my work is very much basic research. However, if you manage to find a cellular mechanism or signaling pathway that is the cause of a faulty differentiation that in turn will lead to a developmental disease, you have taken a big step towards finding a solution. The step that naturally follows, is to find a molecule that targets the faulty mechanism and corrects it. Generally, this is a smaller step.
We have seen that the same cell assays that we use in research to find mechanisms and signaling errors could be used in a screening process for potential drug candidates. In that way, screening could be done at a high throughput rate and hopefully speed up the candidate selection.
Where do you hope to have reached in five to ten years, what are your hopes?
On the research side, I hope that we will find relevant pathways or mechanisms related to developmental diseases of the brain. With relevant, I refer to the fact that they should have a close connection to the actual disease and be the differing factor between sick and healthy patients.
I also hope that cells we are able to derive in my lab will be used by other researchers and benefit their efforts. Everyone has their own expertise and I would really hope to be a catalyzing factor by providing them with good cells.
A part of this comes from the fact that our cells originate from a patient who is kind enough to donate tissue for research purposes. I want that patient to feel that his/her donation will generate as much new knowledge as possible.
Then there is the regenerative medicine side of my research, that is not something I work with personally but I still want to contribute to that field through collaborations. On the other hand who knows if iPSCs will be the most valuable alternative for stem cell therapies in regenerative medicine? Perhaps there will be a more direct route from adult to semi-adult cells for therapeutic applications which turns out to be a much safer alternative. Only the future will tell...
You are back at KI, now as an associate professor. Does coming back from the “forefront” of research and having worked with key opinion leaders put extra pressure on you today?
In some ways yes! Of course, having a good network is very important when performing research at this level and having performed research at high profile labs helps with this. My job description at the moment is split in two, on this side, I have the associate professor title which comes with all the responsibilities of setting up a lab with Ph.D. students and grant applications. On the other side I have been given the task of establishing an iPS cell facility where we will reprogram cells for scientists at the price it would cost them to do it in house. The idea is not to make a huge profit from this facility but rather to offer labs, who lack the expertise, the possibility to reprogram cells.
These roles have different challenges and require different skills! I definitely feel more at home with the former, Anna says with confidence. Planning, performing and analyzing experiments in a lab is something I have done for quite some time now and I am very familiar with that role. As opposed to my second role, I am very new to handling an iPS facility, the economic and personal responsibilities that come with it are new to me.
The facility is more like building a company in the sense that we are looking for customers who are willing to pay for the service and enough customers so that we can pay for the employees and all materials needed. And this has less to do with how good of a scientist I am. Economy and that sort of things are not my competence.
" I do not do research to be a professor I do research because of my passion and curiosity"
Are there any specific challenges when setting up a lab and being a rookie associate professor?
The scientist challenges are of course many. I recognize the environment and is safe in it, but as a new scientist, I have to prove myself, as fast as possible! How do I go about this in the best way? Should we focus our efforts on one large promising project or should we try to go for quantity and speed spreading our efforts and resources over a number of indications? Bigger labs who have less to prove would not hesitate to take on a promising path even though it would lead them on a long journey with publications hitting shelves maybe five years later.
This is a big challenge for me! There is just a short window of time for me to prove myself as a new scientist and a new group leader. What is the most strategic route, is digging a deep hole the better way or stay on the surface and look for easy targets.
Do you have any tips for young scientists who aspire to become the key opinion leaders of tomorrow?
A lot has changed since I did my Ph.D. Back when I was a student I still did not have a clear aim, where would I go next? Even at the end of my Ph.D. when I was to decide whether or not to do a PostDoc I wasn't sure. I did, however, feel that Austins lab was a dream... after reading his publications for a few years it became clear that this was something special, something I really wanted to do.
It was a dream come true when I got to do my post-doc in his lab at Cambridge, but still, I did not have a clear next step in mind. I have been a very one step at the time kind of person. Today I feel that PhDs have such a very tight focus already from the start! There is a plan in place of what skills I need to acquire in order to get to that point later on that I am looking for.
Today I find that many PhDs are looking for mentors to help them find this focus. Mentors are valuable support, but in my career, it is not until now when I have a clearer goal of what I want to achieve, that I have felt the need for someone to guide me and share the experience.
When I started my position here at KI two years ago as an associate professor I felt truly lost for the first time. And now I have the need for many mentors who can provide experience from several fields and points of view. There is the scientific aspect, as I mentioned, which area to focus on, how to get grants for your research and so on. Then there is the leadership role that is new to me, that is not something beeing you practiced during a Ph.D., neither as a student nor a PostDoc.
Is there something specific you would recommend an aspiring student to consider?
One step at a time is my suggestion. Try different areas and find your way by trying different things. Don't push yourself to become a PI if you do not really want it! If you pursue a position as PI purely out of hierarchical reasons it will be very hard. It will be a tough journey if you are not sure of your passion for science, and it is a long journey. I do not do research to be a professor I do research because of my passion and curiosity. Some PhDs today have a strong focus early on, I feel that it might work out, but I fear that you might get burned and lose the passion by pursuing something for the wrong reasons.