"The research results open the door to new hypotheses concerning the ecology and development of networks between proteins and can help in the development of targeted treatment strategies for cancer" says Prof. Barak Rothblatt
An interdisciplinary study applying principles of cancer ecology and biology reveals a structure of a protein network that makes it possible to predict missing links in one type of cancer using data from another type of cancer. The scientists from Ben-Gurion University of the Negev emphasize the importance of research for the development of treatments inside the cancer cells. The research findings were published in the prestigious journal Nature Communications..
A conversation over a cup of coffee between Prof. Barak Rothblatt, a genetics researcher from the Department of Life Sciences at Ben-Gurion University in the Negev, ToDr. Shay is a philosopher, an ecology and networks researcher in the same department, ignited the imagination of Dr. Philosopher. "Barak told me about his research that deals with interactions between proteins and it created a link for me to interactions between species", he shares. "We decided to test a combination of the methods and theories from ecology in cancer research."
This is where the interdisciplinary research started, which applies the principles of ecology to the biology of cancer. The research focused on mitochondria, a small organ inside the cell that regulates its metabolic activity with chaperone proteins. The role of chaperones is to make sure that other proteins function correctly and to prevent their accumulation in an abnormal way. What was not known about the mitochondria, is which proteins depend on which chaperones for their folding, in favor of creating a 3D structure. This figure is significant in light of the fact that this information opens the door to damaging several proteins at the same time. By damaging the chaperone on which they depend, the metabolic activity of the cell can be controlled, just like in cancer treatment.
The researchers hypothesized that if a protein depends on a certain chaperone for its folding, then when the cell increases activity for a certain protein, it will increase the activity of the gene that codes for the chaperone since it is important for the folding of that protein. It is necessary that there is no lack of a chaperone in order to have someone to fold the newly formed protein. For this, the researchers used data collected from thousands of tumors from patients in 15 different types of cancer.
In addition, the theory of ecological networks applied to the protein networks was used, with the help of which a network of chaperones and proteins was discovered which is divided into two groups with connectivity between them.
This network made it possible to conduct a simulation, designed to understand how removing or leaving chaperones affects the stability of the network. During the analysis, the chaperones were removed one by one from the network to quantify its rate of collapse. This method makes it possible to plan a treatment intended for cases where it is necessary to quickly collapse the entire network or to preserve the general structure of the network, while damaging only a certain group of proteins. This understanding is necessary for promoting personalized medicine and directing the treatment to the condition of a particular patient.
Understanding the structure of the network and the interactions between the proteins and chaperones in the mitochondria may enable the development of significantly effective drugs for the treatment of cancer in a targeted and personalized manner, depending on the type of cancer and the specific network structure in the cancer cells in each case.
"What is beautiful about this research is the interdisciplinary nature", he said Dr. Philosopher. "The integration of ecology added to understandings in the field of cancer biology".
"The research results open the door to new hypotheses concerning the ecology and development of networks between proteins and can help in the development of targeted cancer treatment strategies", he concluded Prof. Rothblatt.
This research was supported by the Israel Science Foundation (Grant No. 1436/19 awarded To Prof. Barak Rothblatt and grant number 1281/20 awarded to Dr He is a philosopher), the Cancer Society, and the NIH.
The study included an analysis of data from the cancer genome atlas (TCGA) database and the MitoCarta 2.0 mitochondrial database.
The research group included researchers from the life sciences department at Ben-Gurion University of the Negev in Israel, from the mathematics department at Dermot University in the United States and from the National Institute of Biotechnology in the Negev in Israel. By combining knowledge from different fields, the researchers were able to investigate the structure and stability of the protein network in a comprehensive and in-depth manner.
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One response
Chaperone proteins, not /chaperon/.
The meaning of the word "accompanied"