8.3.2022 | University of Helsinki
A five-year international project is investigating the development of the human pancreas and the onset of diabetes. Researchers at the University of Helsinki are developing novel cell models for this purpose.
The University of Helsinki is involved in an international research project that investigates the onset of diabetes and the development of the pancreas. The project has received a grant of £3.5 million, or roughly €4.2 million, from the Wellcome Trust. A sub-project carried out at the University of Helsinki is headed by Professor Timo Otonkoski, whose research group will receive approximately €1.4 million of the overall funding.
The project is aimed at learning in detail how the development of the human pancreas differs from other species and what the significance of pancreatic development is for insulin production and the onset of diabetes. Serving as a starting point for the project is an observation made at the University of Exeter, according to which mutations in the gene ZNF808 cause a developmental disorder in the pancreas that results in congenital insulin-deficient diabetes.
ZNF808 was born late in the evolution of the human species, and its role is to bind with a specific repeated sequence in the genome and silence the expression of other genes.
“As far as we know, this is the first example of a developmental disorder occurring in humans whose cause is a gene found only in humans. We assume that similar disease mechanisms will be uncovered through further research,” Otonkoski says.
A new cell model helps to investigate the initial development of the pancreas
In their studies, Otonkoski’s group has differentiated human pluripotent stem cells into pancreatic cells. In the new project, the group will utilise its expertise to create the cell models needed in the project. They will also develop novel cell models that researchers can use to explore the initial development of the pancreas.
With the new model, they can accurately observe molecular events that distinguish between the initial development of the pancreas and the liver.
“Our preliminary observations indicate that the ZNF808 mutations affect humans in such a way that the embryonic cells that are supposed to differentiate into pancreatic cells instead develop into hepatic cells,” Otonkoski says.
Top-level researchers join forces
In addition to Otonkoski’s groups, two other research groups are active in the consortium, which is headed by Professor Andrew Hattersley from the University of Exeter. Hattersley’s group focuses on investigating the forms of diabetes caused by the mutations. The group has identified a broad range of new genes that cause diabetes in humans.
Researcher Michael Imbeault from the University of Cambridge heads the third group of the consortium. He is a leading expert in research on genome evolution, and he has already previously investigated the ZNF808 gene.