Once the enzyme has cut the proteins, the laboratory technicians now have a mixture of smaller protein pieces called peptides. These peptides are like small LEGO bricks that are now ready to be studied using mass spectrometry, which measures the different sizes and the electrical charge of the peptides. Describing the peptides requires breaking them into smaller pieces in the instruments to see the differences in their amino acid structure. By analysing the different sizes, researchers can identify the peptides and find out which proteins they come from and how much of them is present. This helps scientists understand the proteins’ function in the body and how they affect human health.
The latest research project in the area focuses on cells from patients suffering from acute myeloid leukaemia, AML, and is a collaboration between Erwin Schoof, Associate Professor at DTU, and Rigshospitalet. Erwin Schoof has received DKK 10 million from the Lundbeck Foundation to establish a research team that will identify what determines the viability of individual blood cells and whether it is possible to specifically develop cancer stem cells for the treatment of patients with leukaemia. The work is based on a combination of cell samples from patients, big data, and advanced computational calculation methods.
Analysing single cells
Since launching the mass spectrometry platform in 2018, DTU has expanded its activities and seen a user increase of 30 per cent. This corresponds to around 80 users in 2022, spread across 140 different projects. It can take one to three weeks before the analysis results are ready.
The good results seen when performing analyses on small cell samples have, in particular, attracted new partners and customers. Until 2018, researchers could only perform analyses if they had larger cell samples, which could consist of both healthy tissue and cells from a tumour. Today, they can perform analyses at single-cell level, enabling specific insight into smaller tissue samples.
The latest development in the field is a technique where researchers and pathologists use a laser and a microscope to cut out a small group of cells.
“By using laser dissection, we can cut out suspicious or diseased cells and get very precise answers via mass spectrometry. In this way, we can find out what happens in the cancer cells, but also read their interaction with surrounding cells, and perhaps find new treatments,” says Pia Klausen, Senior Researcher at Rigshospitalet’s Department of Pathology.
Proteins warn about cancer
Rigshospitalet’s Department of Pathology is the largest of its kind in Denmark and performs a number of analyses using DTU’s mass spectrometry platform. In an ongoing research project, researchers are examining preserved samples from patients who have had pancreatic cancer. By using a laser to cut out cancer cells from tissue samples and the surrounding cells in a separate sample, the researchers are examining whether they can use mass spectrometry to identify proteins that can provide new insight into the development of cancer.
“We hope to be able to use laser dissection and mass spectrometry to find special proteins that can be used, e.g., to predict how patients will respond to a certain treatment. It is currently not possible to find these signatures by examining a person’s complete set of genes using genomic analysis. Cancer is a disease in which mutations play a major role. And although it is possible to map mutations using genomic analysis, they will only give an indication of what can happen. The proteins will tell directly what has happened. In addition, it is the proteins that doctors are trying to target with cancer drugs, and we hope to find new therapeutic targets with our research,” explains Pia Klausen.
In collaboration with DTU, the researchers are currently analysing samples from patients with pancreatic, lung and brain cancer. All three are types of cancer with a low survival rate and few treatment options.