2019 has been an exciting year for the proteomics community at Technology Networks. As the year draws to a close, we’re reflecting on some of the key insights we have gained.
Professor Ruedi Abersold on addressing the technical challenges researchers face in proteomics
The advancements that have taken place in the last decade in the proteomics research field have been enabled by improvements and developments in analytical technologies such as mass spectrometry (MS). Whilst these technologies provide rich data, they can be complex to use and present an array of technical challenges that scientists must face.
Professor Ruedi Abersold told Technology Networks: “I think we are in, or are approaching, the exciting state where these challenges are reasonably well, if not completely, resolved. When we get there, we will be able to more strongly focus on creating interesting new biological or clinical research questions and experimental designs and tackle the highly fascinating question of how we best generate new biological knowledge from the available data.”
Assistant Professor Cristina Paulino on structural biology and proteomics
A by-product of advancements in MS technology has been the emergence of MS in the field of structural biology. Now, structural biologists have an array of state-of-the-art MS tools their disposal to study protein structures. But why is this important?
Professor Cristina Paulino told Technology Networks, “Whilst genetics and biochemistry help in understanding what the physiological role of a protein is, structural biology uncovers what these nanomachines look like and how they are wired.” She adds,”Only then can we rationally understand them and use this knowledge to repair, engineer or block them, for example, by building drugs that only fit this specific machine (structure-based drug design).”
Professor Alexander Makarov on the democratization of MS
As the applications of proteomics extend to a wider range of disciplines and fields, an increasing number of scientists are adopting MS-based techniques. “MS developed from a cottage industry of the 1980s and 1990s into a modern industry like aviation in 2000s-2010s, each new development required larger and larger research and development teams to match the increasing complexity of instruments,” Professor Alexander Makarov says. “All this extends the cycle time of each innovation and also forces us to concentrate on solutions that address the most pressing needs of the scientific community.”
The increasing democratization of MS brings new requirements for instruments, he adds, such as “Far greater robustness and ease-of-use, which need to be balanced against some aspects of performance.”
Professor Alexzander Asea on proteogenomics and precision medicine
The rise of the “OMICS” research field has led to an increased focus on precision medicine, whereby medical treatments are tailored to the individual biological characteristics of each patient. Proteomics plays a key role here, as many drug targets are proteins, and the dysfunction of certain proteins in physiological pathways can contribute to disease.
What does the future look like in this space? Professor Asea says, “The seamless integration of precision medicine into personalized medicine will improve prevention, early detection, diagnosis, and treatment of diseases and disorders. This is achieved by its ability to enhance the understanding of the molecular mechanisms and accelerating the translation of molecular findings into the clinic.”
Dr Martina O’Flaherty, on the EPIC-XS consortium
In 2019, the EPIC-XS consortium was launched. EPIC-XS collaborators consists of a unified network of experienced access providers that are dedicated to the development and advancement of proteomics exploration within life sciences. How will they achieve this?
Dr Martina O’Flaherty told Technology Networks: “Providing the broader proteomics community optimal access to experts in the field, and enabling them to utilize high-end mass spectrometry technology, hardware and bioinformatics tools, will help overcome many of the challenges in proteomics.”
She adds, “EPIC-XS will facilitate this access and will also provide hands-on training for researchers, helping to develop best practice workflow, and will also aid the dissemination of proteomics data into publicly available databases and broaden the expertise of experienced scientists and those new to the field of proteomics.”
Dr Roman Fischer on bottlenecks in clinical proteomics
Proteomics is largely influencing the landscape of modern medicine, a development that Dr Roman Fischer believes is “long overdue”. He believes that one of the biggest breakthroughs in clinical proteomics is be the ability to perform shotgun proteomics in a high-throughput manner, stating, “This marks a step change and is a huge improvement on what was possible not too long ago.
However, we need to be aware that this removes one bottleneck and creates several others, such as sample handling of large numbers of biological specimen or data analysis. Due to increased throughput and robustness, we are bound to see many more clinical studies using proteomics as primary readout.”
Professor Andrea Sinz on cross-linking-mass spectrometry and proteomics
One of the latest methods added to the MS toolbox is cross-linking-mass spectrometry. Briefly, this involves creating a chemical crosslink that acts as a “ruler” and allows scientists to shed light on the three-dimensional arrangements of proteins, protein complexes, and even large protein networks. But there are still challenges in this space. Professor Andrea Sinz says, “The main challenge is in software development. We need to develop software tools that can handle the complicated peptides and cross-linking product mixtures. Software development has made huge progress. Currently the challenge is to have novel reagents and cross-linkers that are cleavable in the mass spectrometer to get the signatures for automated analysis.”
Professor John Yates on the future of proteomics
Proteomics has come so far in the last few decades. But where will it head in the future?
We asked Professor John Yates for his insights: “Proteomics is going to advance in a few areas. It is going to be more sensitive as we push down towards single-cell analysis. It’s going to become more high-throughput so that we can analyze more patient samples and so forth, enabling it to be on par with RNA seq. type strategies.”
He continues, “The scale of proteomics is going to advance to the point where we can obtain an entire proteome in a single experiment. We’re close to this now, and we may actually be close enough,” says Yates.