With the ever-increasing potential of new technology and the exponential growth of the life sciences field, researchers are always running into new problems to solve. In this interview series, we get scientists’ opinions on the ‘Big Challenge’ in their field and the steps being taken to address it. From new and unique hurdles to fresh takes on common problems, we dive into the complexities of the research landscape.
In this interview, we chat to Hanno Steen (Boston Children’s Hospital) about the ‘big challenge’ for proteomics-based analysis of body fluids, such as blood.
FLG: What is your background and role?
Hanno: I am a chemist by training and moved, via analytical chemistry/mass spectrometry, into the field of proteomics, in which I have been working for 25+ years. Currently, I am an Associate Professor of Pathology at Harvard Medical School and run a proteomics research laboratory at Boston Children’s Hospital. In my laboratory, we are particularly interested in developing high-throughput sample-sparing proteomics methods to allow for the analysis of 1000s of body fluid samples even from the frailest patient population, such as extremely low birthweight premature neonates. In general, we are interested in understanding the molecular composition of body fluids, which integrate the secretion of many organs and tissues, i.e., they don’t have a matching transcriptome that we could use as a proxy.
FLG: What is the ‘big challenge’ in your field?
Hanno: The biggest difference between protein-centric and RNA/DNA-centric analytical methods is the absence of general and/or specific amplification steps, i.e., we have to deal with the sample as it comes. This has been particularly challenging for plasma/serum samples, where the 22 most abundant proteins account for 99% of the protein content, i.e., they are ‘drowning out’ many of the lesser abundant proteins in a sample. Additional complications stem from lack of throughput and robust generalizable sample processing methods, which made each sample type a new time-consuming analytical challenge.
FLG: Why should people care about this?
Hanno: Blood is by far the most commonly collected body fluid to monitor health and disease at home, in a doctor’s office or in the hospital. It is a systemic body fluid; it collects the secreted proteins from all the organs and tissues of a body and as such contains information about the (disease) status of all organs and tissues. To improve current diagnostics and to work towards personalized/precision medicine, we have to uncover these organ-/tissue-specific proteins. DNA/RNA-based methods are only of limited use as there is not a single transcriptome that can be correlated with the blood proteome. As such, we have to take a closer look at the proteins, i.e., we have to do proteomics on such samples.
FLG: What is being done to tackle the issue, or what should be done to tackle the issue?
Hanno: The newest generation of mass spectrometers have been instrumental to allow for throughputs in the 100 samples per day range, i.e., 5- to 10-times the previous throughputs. Although a game changer in itself, it is still not fast enough for the envisioned cohorts. Similarly, one has to tackle this throughput issue holistically, i.e., sample management, sample processing, sample analysis and data analysis all have to be streamlined to avoid any bottlenecks.
FLG: What is your advice to people breaking into the field?
Hanno: Proteomics has significantly matured over the last 5 years. Not only mass spectrometry-based proteomics, but also various affinity reagent-based proteomics approaches. The different methods have varying strengths and limitations. As such, it is important that newcomers to the proteomics field inform themselves before picking the ‘right method’ for their respective problem at hand, and number of proteins per dollar is often not the best approach. In short, the best is yet to come as proteomics is finally at a stage where it can deliver what it has promised since its inception/invention.