Discovery by Scientists at the Saha Institute of Nuclear Physics :-
Ten years ago, when biophysicist Abhijit Chakrabarti started looking at telltale proteins in the red blood cells of children suffering from leukaemia, there weren’t many takers for his research.
Chakrabarti, professor of biophysics at the Saha Institute of Nuclear Physics (SINP) in Calcutta, believed that the intriguing protein signatures might, some day, help doctors identify blood cancer at an early stage and customise cancer therapy for each patient, instead of relying on a one-size-fits-all approach.
“Even experts couldn’t relate to the study of proteins for clinical application,” says Chakrabarti. “Those were the heyday of gene discoveries.” Now things have changed dramatically in favour of proteins, the body’s workhorse molecules. Scientists as well as drug makers have realised the limitations of gene-based data.
A series of publications by Chakrabarti and his team in international journals such as the British Journal of Haematology and the European Journal of Haematology is testimony to how quickly the young field of large-scale analysis of proteins — known as proteomics — is growing. The nascent field of research involves efforts at developing methods for sifting through thousands of different proteins in the blood. The goal is to identify the trace proteins — called markers — that are leaked by tumours into the blood, to be subsequently used for early and more accurate diagnosis of cancer and other diseases.
If all goes well, Chakrabarti hopes their work will some day yield simple tests that will allow for early diagnosis of childhood cancers like acute lymphoblastic leukaemia (ALL) — diseases that can prove fatal if not detected at early, and more treatable, stages.
“It is very important, both to diagnose childhood leukaemia as early as possible, and to determine what type of leukemia is present so that treatment can be tailored for the best chance of success,” says Dr Debasish Banerjee, haematologist at the Ramakrishna Mission Seba Pratisthan, Calcutta. “At present the therapy is based on genetic changes in leukaemic cells, which helps in classifying patients into specific risk categories. This is known as risk-based stratification therapy,” he adds.
Haematologists usually deploy gene chips or DNA microarrays to gauge the changes. One big problem with the strategy, however, is that the genetic chips offer a ‘global’ view of cancerous changes, not the ‘ground level’ view in the proteins. “Another very important issue is monitoring the response to a therapy of the diseased cells,” says Banerjee. He believes that the current diagnostic tests fail to tackle these problems. “Proteomics can not only take care of both the problems but also diagnose minimal residual disease (MRD) responsible for a relapse after therapy is complete.”
Chakrabarti’s recent foray — presented at an international symposium on Complex Diseases: Approaches to Gene Identification and Therapeutic Management, in Calcutta — is critical in the search for marker proteins among a vast sea of proteins in blood serum. “It’s like looking for a needle in a haystack,” says Sutapa Saha, a co-researcher. “Blood serum is an extraordinarily complex mixture of thousands of proteins,” she adds.
What’s more, any two proteins may exist in concentrations that differ more than a billion-fold from one another. “Systematically searching for the potential candidate proteins from thousands of others is extremely painstaking work,” says Dipankar Bhattacharya, another researcher involved in the project. After years of persistence the SINP team has been able to hunt down 80 such proteins. The study is scheduled for publication in the journal Proteomics – Clinical Application.
To guide their search, the Chakrabarti’s lab uses instruments like mass spectrometers, which can sort mixes of proteins, based on size, weight and electric charge. Since every protein is different, each has an equivalent of a molecular “barcode” to distinguish itself. The goal, Chakrabarti says, is to find proteins that are present only in the blood of people with cancer or are at detectably higher levels in people with cancer than in healthy individuals.
Chakrabarti is pursuing another approach too in finding cancer-specific markers, based on the immune system’s ability to act as a “biosensor” of disease. “It’s well known that the immune system can recognise cancer cells as abnormal and react against proteins made by tumours,” he says. “One of our approaches in finding proteins made by cancer cells is to see what antibodies or immune cells are produced by the immune systems of people with cancer but are not made by healthy systems.”
Despite the stiff challenges the team faces, drug designers have concluded that protein-based diagnostic tests hold greater promise than those exclusively based on genes, which are the DNA blueprints that cells use to make proteins. Proteins are more relevant to the biological functioning of the cell and most drug targets are found in them. Above all, proteomics assays, or protein-based diagnostic measurements, can be applied to readily available biological samples like serum and urine. “ The current dogma is: to understand genes better you need to read the proteins too,” says Chakrabarti.
Sources: The Telegraph (Kolkata, India)