Thesis defense Helena Viñas Gaza: Tracing histone modification dynamics in single cells during differentiation and early development

Each cell within an organism contains the same DNA code. Yet not all of these cells are the same in appearance and behavior. That is because different parts of the DNA are turned ‘on’ and ‘off’ in the individual cells: the gene expression is different. This affects what the cells look like and what they will do. The regulation of gene expression is important, for example, during the development of an organism and the formation of tissues. The field of epigenetics studies changes in gene expression that occur without changing the DNA code. One of the main epigenetic mechanisms is histone modification.

Exploring histone modifications

During her PhD, Viñas Gaza focused on these histone modifications. “Histones are proteins around which DNA is wrapped to organize and compact it in the cell nucleus. These histones have tails that can be modified by attaching chemical groups to them, making the DNA more or less compact and thus more or less accessible for the cell to use. In this way, histone modifications can change the gene expression of a cell without changing the DNA code,” she explains. Viñas Gaza wanted to develop new ways to study the relationship between these modifications and gene expression. “The details of how histone modifications influence gene expression remain largely unknown and it was very complex to study that with the existing techniques.”

New techniques to study single cells

Therefore, Viñas Gaza developed two new techniques, called sortChIC and T-ChIC, that will enable scientists to advance their understanding of epigenetics. “These techniques allow us to measure histone modifications at the level of a single cell, while simultaneously determining the gene expression of the same cell. This was not possible before and can now be applied in many tissues and animal models. In this way, we can learn more about the effects of histone modifications on gene expression, for example during development and the formation of tissues.” Viñas Gaza used these new techniques to study blood cells and zebrafish. “We gained a deeper understanding of the histone modification patterns of different cell types during the formation of blood cells, as well as of the effect of histone modifications on gene expression during the development of zebrafish,” she explains.

Ups and downs

Viñas Gaza describes her PhD trajectory as a challenging but valuable experience: “At the beginning it’s very overwhelming because you have to get familiar with the team, the techniques, the research field and a new country. Then the pandemic happened and it was difficult to continue being motivated and excited about the work. But with time comes confidence and at the end I have learned and improved a lot personally and scientifically.” Looking back, she sees several highlights: “Being able to present your work internationally, and seeing it published in journals and in your thesis book is pretty awesome. And I also got to learn from very intelligent and talented coworkers with different backgrounds.”

PhD and mental health

When asked for lowlights she says: “I realized the culture in academia needs to improve. Unfortunately, there is a lot of pressure on PhD students, a power-imbalance with your PI, discrimination, a lack of mentoring and empowering, etcetera. I am proud of being part of the first PhD committee with the hope to improve this.” Her advice to new PhD students? “Try to find a good and supportive environment. Communicate well with your PI from the beginning. Be daring to ask questions as silly as they might sound to you. Learn to put limits and most of all try to enjoy it to the fullest but without damaging your mental health on the way.”