What have you been working with during your PhD?
During my PhD in the RNA and Stem Cell Biology research group the overarching question that drove my research has been - how is genetic information regulated in stem cells and cancer cells? My focus was on ribonucleic acid, or RNA, a molecule involved in several key steps of gene expression. We uncovered a novel regulatory mechanism which, through the modification of RNA, controls protein synthesis levels in a unique population of stem cells during the earliest steps of embryonic development and the maturation of blood cells.
The mechanism relies on the chemical modification pseudouridine (Ψ) of specific RNA molecules, which we named mTOG. We found that in the absence of Ψ-modified mTOGs, through knocking out the enzyme responsible for this RNA modification, there was an increased rate of protein synthesis. This ultimately led to hematopoietic stem cells losing their ability to mature into blood cells.
We discovered that loss of mTOGs is very common in hematological malignancies and correlates with a decrease in patient survival. We are now treating blood cells isolated from leukemic patients with mTOGs, to restore a normal rate of protein synthesis and promote the production of mature blood cells, hopefully eradicating the leukemic cells.
The research during my PhD began trying to understand a basic molecular mechanism and we were able to translate this into a project with exciting clinical potential.
How did you end up doing a PhD at Lund Stem Cell Center?
I’ve always had a passion for stem cells. I’m originally from Bergamo, a small city north of Milan. After completing my Bachelor’s degree at the University of Pavia, I moved to Lund to study for my Master’s degree in Biomedicine. I had heard of Lund University as a great place to study molecular and stem cell biology and whilst here was introduced to the research in the RNA and Stem Cell Biology research group, led by Assistant Professor Cristian Bellodi. I initially joined Cristian’s group for a summer project, the work from which was further explored within my Master’s thesis and finally transformed into my PhD project.
What has been the most enjoyable aspect of your PhD?
The people that took part in this journey. At the Division of Molecular Hematology we have a highly collaborative and fun environment. For example, as part of the revisions for the Cell paper that we published in 2018 we had quite a few challenging questions that we needed to address. I have to say that everyone at the division came together to help with these challenges. This was something that was both helpful and really enjoyable, working together with such great people.
What has been the most challenging aspect of your PhD?
The beginning of my PhD was very challenging, as there were a lot of things to learn and I had very little practical research experience. It took some time to adjust. I feel very lucky in that I enjoy doing research, but in the beginning it was challenging to understand the correct mindset to plan, execute and interpret experiments.
What are your plans following your PhD defence?
I have applied for a postdoctoral position at The Rockefeller University in New York to pursue my interest in stem cell and molecular biology. I plan to start this new chapter in the beginning of next year.
Nicola will be defending his PhD thesis titled “Post-transcriptional control of stem and cancer cell fate. New roles for and old RNA modification” on Thursday 24th September at 09:00 at Belfragesalen, BMC D15.
Zoom link: https://lu-se.zoom.us/j/62032380098?pwd=dlVpWVdsQmZaakJZSkhUTUN2STF0dz09
Passcode: 351326
His opponent is Professor Michaela Frye from DKFZ Heidelberg