We understand that most lab websites target a specialized audience, making it harder for non-scientists to understand the importance of our research. However, explaining what kind of projects are launched by institutes, universities, schools, hospitals and also private companies is of paramount importance… not to simply discuss ideas, but because science exists only until we all agree it is an investment for a better future. We present here the focus of our work. Please, write us if you want to know more.

What is epigenetics?

Almost all the cells of our body have the same DNA sequence. We inherit our DNA from our mother and father (half from each), and it never changes even while we develop into a complex organism. The DNA contains all the information to make our cells fully functional, i.e. the genes. However, the cells of our lungs are very different from those of our eyes, and so all other tissues. This is because DNA is read differently in different cell types, and this “interpretation” is kept constant when specialized cells divide. For example a liver cell generates another liver cell when it splits. This is epigenetics: inheritable characteristics of our cells that are not due to the sequence of the DNA.

How does this work? The DNA is tightly packaged around proteins named histones in a structure called chromatin (originally named this way because scientists had seen it by microscopy after applying color staining). The regions of the DNA that are more exposed or “open” are read by the cellular machinery. In different cell types, the exposed regions are different, and that is why the DNA is interpreted differently. We study these histones, and how they are modified to open and close specific chromatin regions.

Onder, Sidoli et al. Expert Review of Proteomics (2015)

Why we study epigenetics at a School of Medicine?

Regulating the structure of the chromatin is a highly intricate process. Many aspects are still unclear; curiosity is already a valid excuse to find out more… Once decoded the mechanisms used by cells to specialize and maintain their specialization, we might be able to understand how we got to be this complex. We could also modify unicellular organisms to produce more efficiently biomolecules used in our daily life, from ethanol to protein supplements.

However, there is also a more practical and urgent reason to study epigenetics. When the fine-tuned epigenetics regulation does not work properly, cells fail to function or grow uncontrolled leading to diseases such as cancer. Epigenetics aberrations are common in many diseases, especially those not caused by external pathogens (viruses or bacteria). We thus work hard on understanding which “cogs” of the machinery are out of control, so we can develop drugs to block them or directly kill those cells.

In addition, understanding epigenetics will open to enormous potentials in surgery. We will be able to modify the specialization of our own cells and generate a new tissue from a small skin biopsy. Imagine the convenience of generating a new tissue from our own cells; we will perform more efficient transplants without the need of donors. Find out more by reading about induced pluripotent stem cells.

What is proteomics?

In our field, whatever ends in “omics” implies the study of the total. Genetics is the study of genes; genomics is the study of ALL genes and how they interplay with one another. Proteomics is the study of all the proteins present in a cell or in a tissue. This is very important, because proteins are responsible to structure the cell (e.g. histones for the chromatin), make reactions (enzymes), transfer messages (hormones) and recognize/fight external agents (antibodies). Proteomics is a very popular discipline in medical science, because diseases have frequently many proteins improperly regulated at the same time. Taking a proteomics approach allows to visualize a global picture on which proteins are different from a healthy cell, so that we can better understand what is wrong and how to fix it.

More in general, science is more and more moving into collecting big data to understand the complexity of networks within a cell. Studying the role of individual genes or individual proteins is still fundamental, but the “omics” are now providing the best perspective to decide where to start. A major aspect of our research is to improve our workflows to make proteomics more efficient and more flexible to study different aspects of the proteome of a sample. Histones are proteins, so our advances in proteomics are reflected in the analysis of histones as well.

What is a mass spectrometer?

The mass spectrometer is our essential and most used instrument when we analyze proteomes. A mass spectrometer is a device that defines the molecular weight of a molecule based on how this molecule “flies” into the analyzer. There are multiple types of mass spectrometers that differ based on how the signal is resolved, but their output is univocal: the mass and the abundance of the analyte. Progresses have made these instruments more sensitive and more capable of detecting and quantifying many signals simultaneously. Therefore, a biological sample like a biopsy or a cellular extract has mass spectrometry as ideal methodology to identify and quantify all the proteins present in the mixture. We optimize methods to acquire signals in mass spectrometry, mostly to detect more informative layers of data about our proteins. For example, we study regulations in protein abundance, protein synthesis rate (turnover), protein localization in the cell, protein interactions (with other proteins or other molecules), protein modifications and protein structure.

Considering that every molecule is made of matter with a quantifiable mass, mass spectrometry is likely the most versatile and applicable technology in science overall. In fact, mass spectrometry is now widely utilized not only to study proteins, but also all other biomolecules in the cell like lipids, nucleotides, carbohydrates and many other metabolites.

Sidoli et al. Journal of Cell Biology (2017)

What is a scientist?

This is (apparently) simple. A scientist is anyone so curious about something to dedicate much of his/her efforts into accurately demonstrating the truthfulness of a hypothesis. Frequently, this hypothesis is the result of observed evidence, of which gathering might require the development of new methods. We develop new methods using our mass spectrometers and other systems to observe new aspects of the cell. Once we identify a new aspect, we collaborate with many other scientists to demonstrate that our observation is meaningful and helps the understanding of a disease mechanism.

A scientist today has many other responsibilities; creating experiments to test a hypothesis is just one of them. We are committed to mentor our colleagues and students. In fact, we need all the help we can find, as the final answer to the question “how we are made?” is bigger than each one of us. We are also responsible to share our discoveries to the science community and beyond, which we commonly do through conferences and by writing papers. It is never simple to balance rigorousness and excitement in front of new findings, so much care should be taken to not confuse incomplete observations with facts. Because of this, part of our duty consists in reviewing our colleague’s work and constructively criticize it when necessary. Finally, most scientists need to work hard to find and obtain funding for their research. Most types of science are still expensive, because hypotheses need to be demonstrated with long and rigorous experiments. Finding sponsors for specific projects is additional effort for us but, in a way, convincing institutions and private foundations about the importance and the urgency of what we do is a very good exercise to keep us focused.