KI-researcher Laura Baranello awarded ERC Consolidator Grant
KI researcher Laura Baranello has been awarded the prestigious ERC Consolidator Grant for her researches into the interaction between the cancer-driving protein MYC and topoisomerase enzymes. Her aim is to identify drugs for more targeted cancer therapy with fewer side-effects. Laura Baranello’s MYCinTOPshape project has been awarded approximately EUR 2 million to be spread over five years.
Drugs that block DNA-topoisomerases, so-called topoisomerase blockers or cytostatics, are one of the linchpins of modern cancer therapies.
Topoisomerases, primarily TOP1 and TOP2, are a group of enzymes that control the internal structure of DNA molecules.
Existing cancer drugs therefor target these enzymes in order to interrupt DNA replication, mitosis or division, in the cancer cell, causing the cell to die.
Treatment damages healthy cells
The problem is that the therapy also damages healthy cells in, for example, the bone marrow, hair and mucosa, which can cause adverse reactions such as a low blood count, hair loss and intestinal discomfort.
"We need to develop new drugs that only block the tumour cells if we’re to reduce the distressing side-effects that patients often suffer," says Laura Baranello, senior researcher at the Department of Cell and Molecular Biology, Karolinska Institutet. "But to get there, we have to know more about the mechanisms that regulate the cellular activity of the topoisomerases."
Dr Baranello’s previous research has shown that the oncoprotein MYC, which has an abnormally high activity in 70 per cent of all human cancers, interacts with topoisomerases and stimulates them to promote the rapid growth of the cancer cells.
"MYC binds to TOP1 and TOP2 and forms a complex with subunits called ‘topoisome’," she explains. "I’ll now be able to use groundbreaking techniques such as advanced microscopy, sequencing, biochemical analysis and drug screening to study how this complex works more closely in physiological and pathological situations."
Recipe for targeted drugs
The research group’s hypothesis is that in blocking the stimulation of the topoisome activity instead of the base function of the topoisomerases they will be able to identify therapies that avoid the DNA damage caused by current chemotherapy.
Dr Baranello’s ERC-funded project MYCinTOPshape therefore also includes screening in order to find other possible drugs that target the unique interaction between MYC and topoisomerases.
"The plan is to produce a new drug specifically able to affect MYC function in the topoisome structure," says Dr Baranello. "Our aim is to be testing the most promising drugs in preclinical models of lymphoma, and eventually in cancer patients, within 5 or 10 years, and in so doing improve both survival and life quality in the people affected."
Grant awarded to 15 per cent of applicants
The ERC Consolidator Grant is awarded to researchers with a research group seeking to strengthen their role as research group leader 7 to 12 years after their PhD.
In the 2022 call, grants were awarded to just over 14 per cent of applicants. Laura Baranello’s project, MYCinTOPshape, is to receive a five-year grant totalling approximately EUR 2 million.