- Materialization of the development of medicine for various diseases, such as diabetes, cancer, neurodegenerative diseases, etc.

- Published in the world-renowned journal, ""Nucleic Acids Research(IF 19.16)""

""Autophagy"" is an essential system to maintain the homeostasis of our body cells during the treatment of diabetes, cancer, neurodegenerative diseases, etc. A new factor that controls this system was discovered for the first time in the world.

Professor Kim Dongha’s team from CUK Medical School’s Anatomy Department announced that it had verified the function of ""C/EBP,"" a new regulator for autophagy for the first time in the world by using single-cell genomics.

Considering that the process of controlling autophagy and discovering its new regulator has been a crucial task in overcoming related diseases, what Professor Kim’s team accomplished in the research is expected to increase the possibility of developing candidate materials of medicine for various diseases which the malfunctioning of autophagy can cause.

As autophagy is a decomposing or reusing system inside a cell that removes unnecessary proteins or damaged organelles to maintain the cells’ homeostasis, autophagy proteins, which are required for autophagy, are also inevitably decomposed in the process of maintaining the cells’ homeostasis. Therefore, it is necessary to generate autophagy proteins by vitalizing the corresponding gene and maintain a sufficient amount of protein in the cell in order to maintain a certain level of autophagy.

However, it is known that serious diseases, such as diabetes, cancer, and neurodegenerative diseases, are caused if this system malfunctions. 

This research of Professor Kim’s team has discovered that C/EBP is an autophagy regulator which operates specifically depending on previously unknown types of nutrient starvation, and it vitalizes related genes by reacting specifically to amino acid starvation among various autophagy-inducing signals.

Especially the autophagy regulator that uses C/EBP’s mechanism, which operates specifically to the amino acid starvation as verified in this research, is expected to be used effectively by targeting the control of amino acids in the development of various metabolic diseases, degenerative brain diseases, cancer or cardiovascular diseases caused by autophagy malfunctioning.

""It is astonishing and exhilarating to successfully complete the research of predicting and verifying a new autophagy regulator for the first time through single-cell genomics for the first time. I want to reflect these approaches in future research of various diseases and verify new factors that cause a disease faster and more accurately, and furthermore, build a foundation for developing a cure for intractable diseases,"" said Professor Kim.

This research was published in the world-class journal ""Nucleic Acids Research(IF 19.16),"" with the thesis ""Systemic approaches using single-cell transcriptome reveal that C/EBP regulates autophagy under amino acid starved condition."" (EOD) (includes reference material and photos).

[Reference material]

Reference 1. Predict new autophagy regulator C/EBP using single-cell genomics

[Reference 1. Details]

In the research of autophagy, we checked the flow of genes which change differently under glucose starvation (GS) and amino acid starvation (AAS).  By analyzing the algorithm, we could predict that C/EBP is the factor that controls the largest number of target genes.

Reference 2. Verification of the new autophagy regulator C/EBP, which operates specifically in amino acid starvation

[Reference 2. details]

After checking whether the C-EBP predicted through single-cell genomics affects the occurrence of autophagy specifically to amino acid starvation, autophagy did not occur (green dots) when C-EBP starvation was induced under amino acid starvation (AAS). However, under glucose starvation (GS), it was confirmed that autophagy occurs easily (greet dots) regardless of C/EBP starvation.

Reference 3. The control mechanism of the new autophagy regulator C/EBP that operates specifically in amino acid starvation

[Reference 3. details]

If amino acid starvation is detected in a cell, the amount of C/EBP protein increases, and the increased C/EBP combines with ATF4 protein. This then directly combines with genes related to autophagy, gene expression occurs and causes autophagy. 

Read the original article ▶