Analytical Research on Cell Response Mechanisms Related to Diseases

At Keio University, the Imoto Laboratory, in the Department of Biosciences and Informatics, utilizes research methods from molecular biology and cell biology, primarily chemical biology, to analyze cell control abnormalities related to cancer and neurodegenerative disorders at the level of genes and proteins. The researchers also aim to develop low-molecular-weight compounds that could become drug leads.

"Our research is in the field of chemical biology. Chemical biology is a research field utilizing compounds to investigate biological phenomena. For example, firstly we look for compounds that can suppress the proliferation of cancer cells, or cause cancer cells to die. When we find such compounds, we investigate why they kill cancer cells or suppress the reproduction of cancer cells, by looking for target proteins of those compounds, and identifying genes that code those target proteins, to find out how the compounds work. That's what the research method of chemical biology involves."

The 60 trillion cells that make up our bodies maintain our normal biological activities through high-level control. Currently, however, much is still unknown about cell control mechanisms. Consequently, analyzing cell control mechanisms is an extremely important research topic for understanding biological phenomena. So, what is this research method like?

"First of all, we collect microorganisms. Our lab currently has seven thousand species of microorganisms. We culture each species, to make a culture fluid. Then, we apply the culture fluid to, for example, cancer cells. In other words, we treat the cells. When we do this, we look for microbes that make cancer cells revert to a normal cell form. We culture those microbes, and we isolate the active substances they contain - the compounds that, for example, convert cancer cells to a normal form. After generating those compounds in isolation, we analyze their structures using NMR and other spectroscopic analyses. If the structures are novel, that's a good thing, and if even some of their effects are new, we're happy. Next, we try to identify the proteins that bind to the compound in cancer cells. Once we've found such proteins, to see whether they're really related to the differences between cancer cells and normal cells, we do a gene knockdown. After checking that, we analyze the genes for those proteins. Then, we look at overexpression; for example, we check whether the cancer is actually cured, or promoted even more. Next, we do cancer control tests of those compounds in animal models, or clinical trials in patients with neurodegenerative disorders."

If this research progresses, the Imoto Laboratory continues to the next stage: developing lead compounds for drugs to treat cancer and neurodegenerative disorders. Each step of the process is analogous to treasure hunting or solving puzzles.

"The first thing we do is look for compounds that could be the seeds for drugs. That really is a treasure hunt. Another aspect of our work is finding out why those compounds have medicinal effects, by analyzing their mechanisms. That's like solving puzzles. Treasure hunting and puzzle solving are very exciting fields of research. So, I hope students will be enthusiastic, and of course, I hope they'll study the basic prerequisites. This is a field that people can be passionate about, so we'll be glad if students participate in this research with us."

 

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