Carolina Guibentif studies embryotic processes leading to disease

SCIENTIST PORTRAIT. Half of all childhood cancers have a suspected prenatal origin, which limits the possibility to study the cells undergoing the initial mutations, as this happens in utero. In her project, Carolina Guibentif propose to use human pluripotent stem cell cultures to study these early events, that take place before birth. Niclas Lundh, administrative coordinator at the institution, has met her.

What is your scientific background?

I became interested in biology when I first came across the central dogma of molecular biology in high school. The notion that there is a “logic” in how cells function, how they respond to environment cues, and how this can cause disease made me want to pursue my studies in this field. I then completed my bachelor and masters’ degrees in Cell and Molecular Biology in Lisbon and Coimbra (Portugal). For my master’s thesis, I joined the laboratory of Dr Malin Parmar in Lund University as an Erasmus student, where I first worked with pluripotent stem cells, and on their differentiation towards midbrain dopaminergic neurons. I then stayed in Lund and did my PhD under Dr Niels-Bjarne Woods’ supervision, this time focusing on mimicking the development of the hematopoietic system using human pluripotent stem cells. At that point, I realized that single-cell profiling was poised to become transformative for understanding mechanisms of development, so for my postdoc I decided to join a world-leading research environment in the field, Dr Bertie Göttgens’ laboratory at the University of Cambridge (UK). There I also gained a lot of experience working with mouse embryos, and was involved in multiple projects where we applied single-cell profiling to dissect the molecular processes driving mammalian gastrulation and early organogenesis.

What are the big scientific questions you are working with? Is there a vision for your research group?

After my postdoc abroad I came back to Sweden to start my own group. For my own line of research here in Gothenburg I am now taking advantage of the expertise I gained during my postdoc, in embryology and development, to better understand the processes that take place in vitro during human pluripotent stem cell differentiation. My general goal is to define cell-fate decision processes, during embryonic development on a molecular level. The main focus is on the development of the blood system, and how things sometimes may go wrong, causing disease such as childhood leukemia.

A broader related question is how well these processes can be recapitulated in pluripotent stem cell differentiation systems. A systematic assessment of this is lacking and would improve and streamline the use of in vitro systems to study development and cellular mechanisms which might cause disease.

In my group we are addressing these questions by combining animal models, cell culture and advanced molecular profiling methods, such as single-cell genomics. Our line of research using single-cell genomics has strong multidisciplinary components, for instance combining experimental developmental biology and computational analysis. Collaborations are therefore essential, but in the long run I also want to foster cross-disciplinary synergies within my group by recruiting talented people of diverse backgrounds and different levels of seniority.

Why did you start with research?

I have always enjoyed solving puzzles, so it was natural to me to do this in a setting that might actually have an impact. Then, as a student I also found it exciting to have the chance to travel and live in different countries, working in different labs and attending international conferences. I was also drawn to academic research by the fact that it is an international environment, I really enjoy being surrounded by people from all over the world who share this same passion.

What co-operations do you have today: with other scientific group, with industry, or clinical?

Presently, I collaborate with other scientific groups, which include clinicians. I don’t yet have any formal collaboration with industry because my research is more on the pre-clinical side and in early days. But when we’ll come across a breakthrough with potential clinical impact it will be very exciting to take it to the next level, towards dissemination and application. I don’t exclude starting a company of my own, but this spreading will be done most likely with an industrial partner.

Could you provide a short description of your research for non-academics?

Half of all childhood cancers have a suspected prenatal origin, which limits the possibility to study the cells undergoing the initial mutations, as this happens in utero. In my project, I propose to use human pluripotent stem cell cultures to study these early events, that take place before birth. Pluripotent stem cells can be cultured in the laboratory indefinitely and can give rise to all cell types in the body. In my lab we establish new in vitro platforms to direct the pluripotent stem cells towards gradually specializing into adult cell types, mimicking embryonic development. This will allow us to study processes leading to disease, such as childhood cancer, as the embryo develops. A better understanding of these molecular processes will help develop novel therapies.

• More information can be found on  Carolina Guibentif´s research page at gu.se.

BY: NICLAS LUNDH