ASPIRE II award to researchers at KI
The Mark Foundation for Cancer Research has awarded an 8 million SEK ASPIRE II Award to the Bennie Lemmens Research Group at the Department of Medical Biochemistry and Biophysics (MBB) at Karolinska Institutet. Supported by a previous ASPIRE I award, the team of Bennie Lemmens established state-of-the-art microscopy and DNA labeling techniques to study how human cells copy their DNA and respond to anticancer therapies, with unprecedented precision in time and space.
Cancer is caused by changes in our DNA that allow cells to multiply uncontrollably. To understand cancer biology, we need to understand how human cells divide and faithfully copy DNA. Every human cell contains roughly 2 meters of DNA, which is tightly wrapped together and packaged into 46 chromosomes to fit all the genetic information into a tiny cell nucleus. Dividing cells need to copy all their DNA within this tight space, and they must do so without making too many errors, as mistakes or damages to our DNA can cause cellular malfunction and lethal diseases such as cancer.
Bennie Lemmens Research Group aims to determine how human cells copy DNA in 3D space. They recently made two innovations that will help to unravel the human genome. First, they developed protocols to efficiently label DNA in multiple colors, which together with advanced microscopy allows them to study DNA replication with high precision.
Creating strings of DNA in human cells
“You can think of our DNA as a ball of entangled Christmas lights, which is hard to study, especially if you want to keep its three-dimensional structure intact. We basically create little strings of Christmas lights in living human cells, and because we know the exact order of the bulbs (e.g. first green, then orange and finally red) we can extract structural as well as kinetics information with nanometer precision”, says Bennie Lemmens, Assistant Professor.
The second innovation is based on 3D tissue expansion, in which the research group physically enlarges human nuclei while maintaining the relative distances between the “lightbulbs”.
“We aim to use these complementary technologies to study how anti-cancer drugs change DNA replication kinetics and how human cells can bypass targeted therapies”, says Bennie.
DNA replication stress is a hallmark of many cancer types, and many therapies used in the clinic today are based on impairing DNA replication. Recent insights reveal direct links between DNA replication stress and the way cancers respond to irradiation, chemotherapy, and the latest immunotherapy drugs.
“Fundamental research is critical to understand the mechanisms driving therapy success and to develop selective and durable treatments for cancer patients we need to find out how cancer cells rewire cell division and escape modern-day therapies”, says Bennie.
“I am proud that we are the first in Sweden to receive an ASPIRE II award and I hope this will inspire the research community to continue their innovative research and join the mission of The Mark Foundation to transform the prevention, diagnosis, and treatment of cancer”, Bennie concludes.
About Mark Foundation ASPIRE awards
Mark Foundation ASPIRE awards support innovative ideas that have the potential to solve high-impact problems in cancer research. The ASPIRE program supports research worldwide, and those who successfully demonstrate proof of concept may be invited to apply for an ASPIRE II award to further develop and expand the research. ASPIRE II awards support 3-year projects with total budgets up to $750,000.
The Mark Foundation for Cancer Research, a charitable organization based in New York City, actively partners with scientists around the world to accelerate research that will transform the prevention, diagnosis, and treatment of cancer. Since 2017, The Mark Foundation has awarded more than $200 million in grants to over 100 academic institutions across 13 countries, with research programs focusing on early career support, team science collaboration, new technology innovation, and therapeutics discovery. Additionally, The Mark Foundation maintains a growing portfolio of investments in early-stage cancer diagnostics and therapeutics companies, including several that have transitioned from grantee projects into commercial development.