ABSTRACT

First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Helena Rannikmae is first author on ‘Mutational inactivation of Apc in the intestinal epithelia compromises cellular organisation’, published in JCS. Helena conducted the research described in this article while a PhD student in Dr Marc de la Roche's lab at the Department of Biochemistry, University of Cambridge, UK. She is now a Senior Scientist in the Complex In Vitro Models group at GlaxoSmithKline, Stevenage, UK, using complex in vitro models to study health and disease.

Helena Rannikmae

How would you explain the main findings of your paper in lay terms?

Colorectal cancer is the third most common cancer in the Western world. A protein called APC has been shown to be involved in the initiation of the majority of colorectal cancers. This protein has been previously shown to be important in regulating cell growth and intestinal tissue structure. By using organoids – three-dimensional cell aggregates that exhibit organ functionality – derived from mouse intestine, we aimed to look for unknown functions of APC. The results of our study reveal a novel role for APC in the intestine in maintaining the shape of cells. Importantly, this is a role of APC that is separate from its other known roles and could therefore potentially be exploited therapeutically or diagnostically to target intestinal cancers.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Organoids have emerged as an excellent in vitro model to study health and disease, and importantly can be genetically modified to monitor alterations dynamically. In our lab, we had no prior experience with organoid establishment or their genetic manipulation. As this project utilized organoids as a model system, there were many technical challenges that had to be overcome. I attended workshops and conferences, and reached out to researchers at the University of Cambridge to learn all the tricks and tips of working with organoids. Communication with other scientists, eagerness to learn a new technique and perseverance helped me build up the expertise relatively fast.

“Communication with other scientists, eagerness to learn […] and perseverance helped me build up the expertise relatively fast.”

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

I remember the moment when I added doxycycline to organoids that were transfected by electroporation with a doxycycline-inducible shRNA targeting Apc and an mCherry expression vector. I clearly remember the moment when I saw red organoids that had changed their morphology to a spherical shape under the microscope. That proved to me not only that were we equipped to genetically manipulate the organoids, but that we were also able to replicate previous findings that silencing of Apc leads to a change in intestinal epithelial morphology. This model set the scene for asking further questions about the consequence of loss of Apc in intestinal epithelia.

Why did you choose Journal of Cell Science for your paper?

We chose Journal of Cell Science because it publishes high-quality articles that cover a range of basic biology topics with impactful findings. We believe that publishing in Journal of Cell Science provides us an excellent forum for communicating our research to a wide audience of scientists.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

I think having a mentor during your research career is very important and, unfortunately, often underestimated in academia. Somebody who listens, motivates when needed and guides is crucial for you to provide the best version of yourself to research. I have subconsciously always looked for a mentor in each of my career paths. I have been lucky to have several people who I would consider mentors and who have shaped my career and research interests. Dr Johan Jirholt from AstraZeneca was one of the first people I considered a mentor, and he influenced me to always look for one as my scientific journey continued.

Mouse intestinal organoid showing loss of budding structures upon depletion of APC, trackable by red fluorescence expression.

Mouse intestinal organoid showing loss of budding structures upon depletion of APC, trackable by red fluorescence expression.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

I come from a family of academics and have therefore always been around conversations about science from a young age. I also had the privilege to travel a lot in my youth and experience different cultures. I was attracted to a career in science due to the way we as researchers explore the unknown and question the already known. In addition, a career in science allows travelling and meeting different people from different cultures.

What's next for you?

I have always been interested in translational research, and therefore took on opportunities both in academia as well as in the pharmaceutical industry before starting my PhD studies. After finishing this research project as part of my PhD, I wanted to utilize my knowledge of organoid models for a direct translational application and therefore joined GlaxoSmithKline as a Senior Scientist in the Complex In Vitro Models group.

Tell us something interesting about yourself that wouldn't be on your CV

Many unsuccessful experiments during my PhD studies attracted me to engage in activities like hiking and team sports, where I could get the energy to persevere and push harder. My growing love of hiking took me to the summit of Mount Kilimanjaro in a blizzard during my third year of PhD studies.

Helena Rannikmae's contact details: GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.

E-mail: helena.rannikmae@gmail.com

Reference

Rannikmae
,
H.
,
Peel
,
S.
,
Barry
,
S.
,
Senda
,
T.
and
de la Roche
,
M.
(
2021
).
Mutational inactivation of Apc in the intestinal epithelia compromises cellular organisation
.
J. Cell Sci.
134,
jcs250019
.