Exploring Cancer drug treatment through the lens of The Powerhouse of the Cell: My Journey with the HiLIFE Research Trainee Scholarship

From the very early days of my scientific curiosity, mitochondria have always held a special place in my heart. Not just labeling it as the powerhouse of the cell, but as a key to understanding our very essence, our homeostasis, and heritage. The  Helsinki Institute of Life Science (HiLIFE) Research Trainee Scholarship allowed me to delve deeper into this fascination, offering me a unique traineeship across two distinguished labs at the University of Helsinki.

What is HiLIFE:

The  Helsinki Institute of Life Science (HiLIFE) is an international institute where outstanding researchers across the University’s campuses solve today’s grand challenges in health and environment together.

The Battersby Lab Experience

My initial month at the Battersby Lab at the Institute of Biotechnology was an enriching experience of learning and exploration. Here, I was introduced to the intricate world of RNA-seq data analysis, specifically focusing on the cellular response to mitochondrial protein synthesis quality control defects. The cells of interest were cultured mouse fibroblasts (MEF), and the conditions involved knock-in mutations in AFG3L2 with matching wild-type control. The aim was clear: identify differentially expressed genes in MEF AFG3L2 KI/KI. The entire process, from data analysis to pathway analysis, was a revelation, and it provided me with a foundational understanding of the techniques and tools used in RNA-seq data analysis.

The Kallioniemi Group Experience

Transitioning to the Kallioniemi and Paavolainen’s group for the subsequent three months, I got exposure to a high-throughput lab environment. Here, I embarked on a research project under the guidance of Dr. Isabel Mogollon Figueroa at the Institute for Molecular Medicine Finland (FIMM). The project spanned from basic cell culture techniques to advanced analysis using data collected with the Opera Phenix microscope and GSEA analysis.

The Kallioniemi Group, specializes in precision systems medicine. In collaboration with Dr. Lassi Paavolainen’s group, they have made significant strides in bioimage profiling using AI tools. One of the recent publications of their collaborator, the Carpenter group of the Broad Institute, published in Nature Methods presented a dataset correlating gene expression data with Cell Painting imaging data. This dataset became the foundation of my project, aiming to characterize novel compounds/genes affecting mitochondrial morphology and function in cancer cells.

The project had specific aims, both in silico and in vitro. The in-silico analysis focused on data mining and big data analysis, identifying relevant genes affecting mitochondrial morphology based imaging features as potential drug targets. The in vitro work involved culturing the renal cancer cell line 786-O, optimizing it for the Cell Painting assay, and performing drug testing using custom-designed drug plates.

The learning curve from the project:

I learned some very important techniques, like cell culture, Cell Painting and western blotting. One of the key aspects was that I learned to approach a scientific question of my topic of interest through completely different perspectives. In the case of Battersby lab, the approach was more towards understanding biology, whereas in the case of Kallioniemi group, it was more centered towards drug testing.

Conclusion

My journey with the HiLIFE Research Trainee Scholarship was not just about learning techniques and conducting experiments. It was about understanding the profound impact of mitochondria on our health and exploring the potential of modern biotechnological tools to unravel its mysteries. As I reflect on my experiences at the Battersby Lab and the Kallioniemi Group, I am filled with gratitude for the opportunities I’ve had and excitement for the future of mitochondrial research.