“I want to understand how a cell behaves like a micro-computer”
We sat down for a virtual chat with Igor Adameyko, Associate Professor at the Department of Physiology and Pharmacology, to discuss his latest research and life questions, how to be happy in science, and to understand more about the person behind the successful ERC Synergy Grant project: ‘Kill-or-Differentiate’.
What’s your WHY?
“I have a very broad question that I am trying to answer during the last several years. I would like to understand how information is integrated in live organisms, at the level of cells. Basically, I want to understand how a cell behaves like a micro-computer, how it computes its state so that it can perform its functions. A cell can be good/healthy, or it can change and transform to an abnormal state. We know very little about how cells make decisions- right? Cells always make decisions during embryonic development, cancer progression, as well as in situations where they are responding clearly to some form of stimulation (e.g., a neuron firing). Although we have many physiological insights in many of these things, we lack some form of systematic knowledge of how cells process information.
This is my biggest question, and I am trying to understand different parts if it by working with different systems. I am interested in pathological conditions, primarily because I want to understand how pathological decisions fall under the ‘wrong decision making scheme’ of the cells. What is it that makes such a decision wrong? We have different ideas about some form of faulty plasticity when cells cannot decide their own fate and that pre-conditions them for tumorigenesis. This is in many ways linked to the question where does cancer originate from? We know many mutations and landscapes that can promote cancer or can help cancer cells to go beyond all the check points. What is the primary thing that changes in a specific cell that makes it become different from the others.”
Igor Adameyko’s background is in developmental biology. Having extensive embryology-based experience, it is only natural that the lab continues on this path today by exploring the origin of norm and pathology, congenital diseases and paediatric cancers arising in the early or late embryo. “We believe that our knowledge of embryonic development is extremely helpful, as it is exactly the time when cells (i.e., different cell types) experience a diversity of phenotypic states and transitions between such states. During development, cells change enormously, and the genetic programmes that are utilised by these altering cell states are later exploited by the cancer cells as well. Many tumour types show the developmental aspects in their dynamics, partly resembling a developing organ or an assembling tissue- as they try to replay aspects of developmental processes. This is where we think our ongoing work and understanding could come in and be useful.” He expressed how the motivation would ultimately be to apply the knowledge gained through this process to improve human health; bridging the gap between developmental biology and regenerative medicine.
The lab philosophy
“The diversity in projects conducted by the lab is not geared towards cancer-discovery per se. We wish our research to be broad, as this is the way we approach the philosophy of science. The aim is to enjoy science, and the process that comes along with it. Cancer becomes a valuable niche in our efforts and forms a part of this diversity.”
Igor begins to elaborate on the lab’s philosophy by describing the arduous process a scientist must go through whilst working on different projects over the course of many years. However, it is only through this process that this scientist begins to develop a knowhow and, in some ways, a pace to tackle incoming challenges with greater ease. “This inevitably will result in a more open mindset, along with more experience and confidence to ask new questions and begin from scratch. This cycle repetition makes science interesting, and fun for us” he states. Interestingly, his lab has shown a real knack for this type of scientific process. Stumbling into cancer was not by accident; as he clearly stated to us: “we came into this field as we had something to say, and we had an insight that could be used for the benefit of the cancer field and more importantly for cancer patients”. This is how the Adameyko lab prefers to embark on new endeavours- which keeps things fun for all his group members whether discovery motivated or those focused more on the fundamentals.
What will we only know about you after we’ve worked together for a year?
“We are a laboratory of friends. We share a lot of social activities; we know each others hobbies and at the same time we share a passion for the projects that we do. We brainstorm together and work very closely. We have a flow and this means that we have fun together” he said with a smile on his face. He followed with “they learn about the lab, the environment and ultimately me”.
Another very important topic emerged from our discussion and this was: “how to be happy in science? This is actually a very important question. We try to run science as a social enterprise. We have the belief that science exists for people not that people exist for science. We are the primary people that experience science, and we should also become happy from it. If we are not happy from it, then we are doing something wrong”.
ERC Synergy Grant
“Our project grant is focusing on neuroblastoma- a devastating paediatric cancer. There is a huge unmet clinical need as almost 50% of children that are positively diagnosed die. This cancer, which arises from the sympathetic nervous system, has some type of embryonic origin starting during the neural crest differentiation stage towards the sympathoadrenal cells. Given our domain speciality (i.e., neural crest cells during embryonic development) we believe that we will have some interesting new ideas to understand the origin of neuroblastoma and ultimately fight it.”
In close discussions with colleagues and collaborators the Adameyko lab became interested to understand the evolution of these tumours and arrived at the idea that these tumours are very heterogenous. This in effect results to tumours having a dense population of varying cell types.
“Most cancer types are heterogenous which means that drugs designed to kill cancer cells are actually designed to kill the most dominating population of cancer cells- those that are easily recognisable. These could be sampled directly from a patient and maintained as an immortalised cell line followed by multiple drug screens against this particular cell line. In reality, it is very difficult to kill all populations of cancer. You can significantly downregulate and ALMOST eradicate it, but there will inevitably be a minimal residual disease left behind that can recover the major population at any given moment in time.” This is where the knowledge of developmental biology kicks-in.
“Understanding how cell-to-cell interactions work, we can direct cell phenotypes and control them. Our aim is not to kill cancer cells; we want to control them and ultimately shift cell types in the tumour to more benign and less metastatic states. Even if the tumour remains, it can be removed by a surgeon, for example, faster than it could ever metastasize, and therefore provide a full cure to the patient. This is a good strategy.”
Most of the pharmacological companies do not screen for such things- “because if you think about it, how would you actually design these screening platforms for such a control? You will need to have some intellectual insight. This intellectual insight can come from single cell transcriptomics studies blended with developmental biology, and from knowing how cell states change, and what directs these changes.” This is the path that Adameyko and his collaborators are going to take for the ERC Synergy Grant; in order to understand how microenvironment can maintain and direct cell phenotypes in cancer, as well as utilise this knowledge to make tumours more benign.
Cancer-related initiatives to look out for?
“We are not yet connected to any large national or international cancer networks. We have some close collaborators, and we know relevant individuals that we are working well with. In general, we are not engaged in any large-scale initiative- yet. There are workshops, symposia, a strong and diverse neuroblastoma group here at the Karolinska Institutet, and The Swedish Tumor Microenvironment (STorM) network initiated from Lund that we know of.” Adameyko’s lab looks forward to meeting people and seeing how the landscape evolves.
Reflections: what would you advise your younger self about research?
“I would say that there is no uniform advice- as different people have different motivations for joining research. Research is a personal battlefield. It is extremely demanding and it’s a lot more demanding than other professions. It could perhaps be compared to professional sport or being a professional artist; so competition is fierce and the struggle will never end”. Igor has quite a lot to say about this topic- this not only showcased his dedication to science but also that researchers must truly love what they are doing and be happy with their choices. He continues by saying that every question posed must become a problem that you are passionate about solving. Afterall, the point is to become a leader, not merely a follower of another person’s question.
“Research is a hobby which you are getting paid to do. This does not mean that you should be getting underpaid or treated badly but if you want to lead your life to be productive and fantastic, you have to develop a deep passion inside of you, and you have to follow it and not agree to any compromises.”
If we [Cancer Research KI] could wave a magic wand and do anything together, what would that look like?
“KI is a strong place when it comes to local environment, fantastic people and collaborations. However, one of the biggest challenges faced by researchers at KI is that nearly everything runs on soft money. Many labs are not sufficiently funded by the institution itself, including the salaries of the PIs, and this model has been predominant for over ten years now. This means that young and more accomplished researchers do not feel secure and cannot project into the more distant future. For example, you cannot plan for a really demanding project that would stretch for more than 4-5 years, and many cancer-related fundamental ideas and searchers do indeed stretch beyond that. How can we work on something important and fundamental when there is no guarantee about whether or not the lab would even still exist beyond 4-5 years at all. KI and/or Cancer Research KI need to work to improve the situation when it comes to having good prospects, stability, and survival. I wouldn’t ask for a lot of money for demanding experimentation - this would be, most likely, impossible even with a magic wand. The overall attitude should change- otherwise competitive researchers will leave to places that have more vision for the stability of strong groups and their perspectives in the future. It should not just be about short-term money and projects.
Perspective is important- if Cancer Research KI can help with ensuring some type of perspective and optimistic outlook for the future that would be good.”