Thesis defense Buys de Barbanson: “Exploring the universe of single cells using multi-omic approaches”

In both unicellular and multicellular organisms, no individual cell is completely the same. The tissues of humans and other animals are composed of various cell types, each with a different function. Even within one population of a specific type of cell, all individual cells differ from one another on multiple molecular levels. These differences are introduced during cell division, for example through DNA mutations or changes in the structure or packaging of DNA. In other words, the cells become more unique step by step. Diseases such as cancer can start in an individual cell when it quickly diverges from its predecessor through cell divisions, and gives rise to a tumor.

Chromosome loss in colorectal cancer

Buys de Barbanson’s thesis provides more insight into various modalities of individual cells. Together with his colleagues, he used organoid models of colorectal cancer, which are tiny 3D structures grown in the lab that mimic the disease. The researchers used advanced techniques to perform multiple measurements in individual cells to reconstrue the order in which chromosomal abnormalities occur in this type of cancer. Because of the integrated measurements, they were able to measure changes that occur in parallel in different cells within one population. Using this method, they found a recurring loss of chromosome 4 that only occurs after the loss of chromosome 18. These findings coincide with clinical observations in patients with colorectal cancer.

Blood formation

Additionally, De Barbanson describes a new technique called scSort-ChIC in his thesis. This technique measures histone modifications in individual cells. Histones are molecules around which DNA is wrapped. Modifications in these molecules influence which parts of the DNA in that cell can be read and thereby influence the proteins that the cell produces.

De Barbanson and colleagues applied scSort-ChIC on blood stem cells and adult blood cells in the bone marrow of the mouse to gain insight into the histone modifications that occur during blood formation.

State-of-the-art technology

Last but not least, he introduces a new technique that can measure various modalities – including histone modifications and DNA structure – simultaneously in an individual cell. De Barbanson describes the validation of this state-of-the-art technology and its application on a system in which the position of every cell in the cell cycle can be measured precisely. He uses this information about cell cycles to integrate the data of multiple histone modifications and compare their behavior throughout the cell cycle.

The work described in De Barbanson’s thesis contributes to our fundamental biological knowledge. In the future, the advanced techniques that he and his colleagues developed may be applied in a clinical setting.

Own bioinformatics company

“Doing a PhD was quite challenging. Especially working with the data of individual cells can be difficult, as the data is generally very sparse and noisy. But it definitely allowed me to learn a lot over the past years. The experience I gained from my PhD even enabled me to start my own bioinformatics company,” says De Barbanson. “If you are just starting out with your trajectory, I would advise you to have plenty of collaborations,” he concludes.

He will celebrate obtaining his PhD with a quiet walk in the forest.