Researchers study how cell division cycles are regulated – ScienceDaily

Maria Cuitino, Ph.D., and her colleagues used animal models and in-depth learning tools to measure protein levels and expose previously unknown cellular mechanisms. to be estimated by cell culture systems. The results begin to identify the first possible events badociated with uncontrolled cell division, a key step in the early progression of cancer.

Previous research has revealed which molecules force cells to divide or not, but this has left many scientific gaps. As bodies are made up of many types of cells that come together to form complex organs, studying the whole body at once can be very complicated, but can also be very exciting and revealing, says Gustavo Leone, Ph.D., Hollings Cancer Center Director and corresponding author of the study.

Previous studies of individual cells in in vitro cell culture systems have provided basic responses to biology within the cell, but omitted the interactions that occur when all cells work together to to form organs. The conclusions of Leone and her team confirmed at least 80% of previous knowledge from cell culture systems and addressed important new questions that needed to be answered.

"Do not know where and when" and on "cell division switches are cast, it's like having paint without canvas." We now have the canvas, and thus the cellular context, about how these proteins behave in the body's cells, "Leone says.

The five-year project probed "when" and "where" a critical family of transcription factor proteins (E2F family) is expressed in mammalian cells. Mammals have at least nine different E2F transcription factors that have activation (activated) or repressive (deactivated) functions. All units in the cells must function properly to constitute a functional organ. "Our DNA provides the code for making the multiple proteins, which are the functional units of our cells." Transcription is the first biological process that makes proteins from DNA, and transcription factors are the switches and off of this process, "says Leone.

Cancer is one of the most common diseases when cells multiply in an uncontrolled way. Understanding on / off switches, transcription factors, is essential for understanding pathological processes such as cancer.

Instead of studying the regulation of cell division in cells in culture (or in vitro), the researchers used a whole organism approach. Two major discoveries were made in this study. The most surprising discovery of this work is that the same family of E2F proteins is organized into two modules that function in a similar way in all cell types and organs of our body. "So it appears that a universal mechanism has been developed to control cell divisions, regardless of the variety of cell types that exist in our body," he said.

The second discovery was the development of tools allowing this level of precision in the badysis of proteins in complex tissues. Thierry Pecot, Ph.D., a researcher at the Hollings Cancer Center of the Cancer Research Center at the Hollings Cancer Center, has been instrumental in developing artificial tools developed as part of this study. "Being able to develop tools for detecting the infrequent presence of transcription factors in each cell and quantifying them is both clinically and biologically relevant," says Pecot.

The Leone laboratory harnessed the power of artificial intelligence to quantify transcription factors in many mouse tissue cells. Although in-depth learning tools have already been used for medical imaging, they were not advanced enough to recognize individual cells on microscopic images within tissues / organs. The technology used by the laboratory is similar to the way that autonomous cars recognize objects in the street and allow the identification of individual cells.

Often, the exact clinical relevance of a particular biological discovery is unclear for decades. Currently, other articles and emerging data from this group provide insights into the role of E2F in cancer. The Leone laboratory has discovered that three transcription factors (E2F3A, E2F8, E2F4) act together to control cell division, while two others combine to stop cell division. These results provide a solid foundation for further studies aimed at understanding these complex mechanisms.

This research funded by the National Institutes of Health was conducted by an international team of researchers with extensive training and expertise, with the lead authors from Argentina, France and China, resulting in a wide variety of processes. of reflection and determination, explains Leone. "Solid, elegant research leads to more questions, and this is certainly true in this in-depth study of E2F transcription factors in mammals."

The study raises important questions for future research, says Leone. Using advanced technology, "we have discovered where and when switching on / off modules for cell division are expressed in intact organisms". However, we do not know why there are multiple switches enabled and disabled and whether these switches have redundant roles. "