Nature: New methods for tagging proteins help track disease

Scientists at the Francis Crick Institute and Imperial College London have developed a new way to study proteins released by cells, which could lead to new tools for
tracking diseases, including cancer.

Biomarkers are invaluable tools that enable doctors to study biology and disease, for example, diagnosing diseases from blood or tissue samples, predicting whether a treatment will work for an individual, or observing how much of a drug reaches diseased cells
.

However, finding these biomarkers is challenging
.
To help diagnose disease, scientists need to identify proteins
that are unique to diseased or cancerous cells and not released by healthy cells.

In their study, published today (Oct.
25) in the journal Nature Communications, the team developed a new method that can identify proteins released by specific types of cells, even if those cells live in a complex environment
with many other types of cells.

"When you have a sample that contains different cell lines, it's hard to identify proteins
from a particular cell line.
Of course, in the lab, we can experiment with just one type of cell, but these conditions do not reflect what happens in the body, and the complex interactions between cells may affect their behavior and thus the proteins they release," explains
lead author Ben Schumann and group leader at Crick and Imperial.

At the heart of the new method is the chemical tagging
of sugar molecules added to cells.
While all cells absorb sugar, the researchers genetically modified the cell type they wanted to study, and only this type of cell would add sugar to proteins
.
When cells make these proteins, they still carry chemical tags, which means researchers can identify them
.

The method uses bioorthogonal or "click" chemistry, which was awarded this year's Nobel Prize
in Chemistry.
One of the recipients of the award, Kablin Bertoz of Stanford University, is a co-author of the study
.
The chemical tag was chosen so it could "click" with another molecule, helping researchers isolate the desired protein or add fluorescent tags
to them.

The researchers demonstrated their method, called bioorthogonal cell line-specific glycoprotein labeling (BOCTAG), which worked well in cell cultures across multiple cell lines as well as in mice, where the researchers successfully labeled proteins
for specific cancer cells.

"In this study, we looked at proteins produced by cancer cells, but our approach could also be applied in other fields, including immunology or infectious disease research
.
" It can also be used to better understand disease biology, including how tumor cells change through complex interactions in the body," said
Anna Sios, first author and postdoctoral training researcher at Crick University.

Ben added: "The next step for our team will be to continue to develop this approach and learn more about how cells produce different proteins
depending on their environment.
"

Journal Reference:

1. Anna Cioce, Beatriz Calle, Tatiana Rizou, Sarah C.
   Lowery, Victoria L.
   Bridgeman, Keira E.
   Mahoney, Andrea Marchesi, Ganka Bineva-Todd, Helen Flynn, Zhen Li, Omur Y.
   Tastan, Chloe Roustan, Pablo Soro-Barrio, Mahmoud-Reza Rafiee, Acely Garza-Garcia, Aristotelis Antonopoulos, Thomas M.
   Wood, Tessa Keenan, Peter Both, Kun Huang, Fabio Parmeggian, Ambrosius P.
   Snijders, Mark Skehel, Svend Kjæ r, Martin A.
   Fascione, Carolyn R.
   Bertozzi, Stuart M.
   Haslam, Sabine L.
   Flitsch, Stacy A.
   Malaker, Ilaria Malanchi, Benjamin Schumann.
   Cell-specific bioorthogonal tagging of glycoproteins.
   Nature Communications, 2022; 13 (1) DOI: 10.
   1038/s41467-022-33854-0