Dr. Poschet, metabolomics offers a dynamic view of cellular processes. What are some of the most exciting applications of metabolomics you've encountered in your work?
Metabolomics has indeed opened up dynamic perspectives on cellular processes, and some of the most exciting applications I’ve encountered are in the field of translational research towards precision medicine. One of the most promising areas is the use of metabolomics to tailor treatments, particularly in oncology. By analyzing the unique metabolic profile of tumors, personalized therapies could be developed that target the metabolic vulnerabilities of specific cancer types. This level of precision will hopefully lead to more effective treatments and fewer side effects for patients.
Additionally, metabolomics is being integrated with other 'omics' technologies - such as genomics and proteomics - to provide a more comprehensive view of cellular function. This integrated approach is transforming our ability to predict disease progression and develop targeted interventions.
As the manager of the MCTP, you support researchers with diverse metabolomics projects. Can you share some examples of the unique challenges and rewards of working in a core facility environment?
Working in a core facility like the MCTP is both rewarding and challenging. One of the key rewards is the diversity of projects we support. We collaborate with researchers from all biological and medical disciplines across Heidelberg and Mannheim, but also from other research institutions in Germany, and even international groups. Therefore, every day presents new scientific questions and opportunities to apply metabolomics in creative and exciting ways. The ability to help push the boundaries of knowledge across such a broad spectrum is very fulfilling.
However, there are significant challenges, particularly when it comes to the structural and resource-related issues that core facilities face. One of the most pressing concerns is the shortage of qualified personnel. Core labs often struggle to secure enough staff, and when we do, many positions are short-term contracts or temporary only. This lack of job security can discourage talented scientists from pursuing a career in core facilities, as they may opt for more permanent positions in industry where they can find better compensation and long-term stability. This brings me directly to another major challenge: Retaining qualified and well-trained staff. The private sector often offers significantly higher salaries and more attractive career paths, leading to a 'brain drain' where highly trained individuals move to industry. This is particularly problematic for core labs, where maintaining expertise and continuity in service is crucial for running complex platforms and providing high-quality scientific support to researchers.
A further issue is the lack of centralized funding. In many institutions, core facilities have to rely exclusively or to a high degree on user fees and project-based funding, which makes it difficult to cover essential costs such as maintenance contracts for expensive equipment. Without adequate funding, we run the risk of equipment downtime, which not only affects the quality of research but also slows down scientific progress.
Lastly, there is sometimes a lack of appreciation from both institutional leadership and the broader scientific community. Core facility scientists are sometimes viewed as 'support staff' rather than equal collaborators, which can lead to a perception that our contributions are secondary. This undervaluation is reflected in everything from career progression opportunities to the recognition of our scientific work. But in reality, the expertise and innovation that core facilities bring are essential to the success of many research projects as I can tell from own experiences in projects that could not have been published or would have failed without the support provided by our great team.
Despite these challenges, the ability to contribute to a wide range of cutting-edge scientific discoveries and to facilitate research that would otherwise not be possible remains incredibly rewarding.
You named already some challenges, I think we can all agree, that sample collection and preparation are critical steps in metabolomics. What are some of the key considerations for ensuring reliable and reproducible results?
Absolutely, sample collection and preparation are indeed critical steps, and ensuring reliability and reproducibility requires careful attention to several key factors.
First, consistency in sample collection is essential. Variations in how and when samples are collected, as well as environmental factors such as temperature or time to processing, can significantly alter the metabolite profile. For example, fasting or non-fasting states, circadian rhythms, even the stress levels and the entire lifestyle of subjects can affect metabolite levels. Establishing strict protocols for sample collection is crucial to minimize these variables.
Second, sample storage is another important consideration. Many metabolites are unstable and can degrade quickly if not stored under optimal conditions. This means samples should be rapidly frozen, stored at -80°C, and processed as quickly as possible to avoid unwanted metabolic activity that could generate false and non-physiological results.
Third, sample preparation must be performed as standardized as possible. The choice of solvents, the method of extraction, and how samples are handled can all introduce variability. In that regard, automation of as many steps as possible can highly improve final results. Using internal standards and quality control samples throughout the preparation process is also beneficial and critical for detecting any potential batch effects or inconsistencies.
Finally, I would emphasize the importance of quality control measures throughout the workflow. This includes not only the use of internal standards but also regular calibration and maintenance of the instruments and incorporating positive and negative controls or QC samples to monitor for technical variation. Adhering to these practices is essential for ensuring that your metabolomics data is both reliable and reproducible across different experiments and laboratories.
As a user of PAL Systems and other automation platforms, where do you see automation in the field of metabolomics or even mass spectrometry?
Automation is a clear game-changer in metabolomics and mass spectrometry, and platforms like the PAL System are a key part of this transformation. One of the most significant impacts of automation is its ability to handle high-throughput analyses, which are critical when dealing with large-scale studies or clinical samples. Automation not only improves efficiency but also reduces potential human errors, which is essential for maintaining data consistency and results quality in metabolomics.
Looking forward, I see automation playing an even bigger role in a few years. Automated systems will likely evolve to handle increasingly complex workflows, integrating sample preparation, data acquisition, and even preliminary data analysis in a single seamless process. In particular, combining automation with AI-driven software could lead to fully autonomous workflows, where decision-making for scientists on sample processing and data analysis will be supported based on initial data outputs and thereby accelerated and improved.
Furthermore, with regard to one technical trend of the last years which is the ongoing miniaturization of basic and simple-to-use mass spectrometry instruments, I expect automated platforms to become more portable and accessible outside of traditional lab settings. This could open up new possibilities for environmental monitoring, on-site clinical diagnostics, and personalized medicine.
Can you describe a specific metabolomics study conducted at the MCTP that highlights the importance of collaboration and expertise in achieving meaningful results?
I would prefer not to highlight a single study, but rather emphasize the research consortia that our core facility has been, and continues to be, involved in. For instance, one of the most significant examples of collaboration was within a highly successful local research consortium on 'reactive metabolites as a cause of diabetic late complications.' In this project, several world-class biomedical research groups from the region worked closely with the technological experts at the MCTP and clinics in Heidelberg. Together, we explored the interplay and role of reactive metabolites, as well as key central carbon and nitrogen pathways, within the framework of diabetes research. These collaborations led to numerous important publications, both in basic research and applied fields.
Currently, our team is contributing to a research consortium aimed at developing a mass spectrometry-based pipeline for the improved prediction of cancer recurrence across various cancer types. Several joint publications have already been produced, and we anticipate more valuable contributions to the fields of metabolomics, proteomics, and clinical medicine in the near future.
Looking ahead now, how do you see the field of metabolomics evolving, and what are the implications for core facilities like the MCTP?
The field of metabolomics is evolving rapidly, and in the next decade, I expect significant advancements in both technology and applications. One of the most exciting areas of growth where my team is also involved is the integration of multi-omics approaches. Metabolomics will increasingly be combined with genomics, proteomics, and transcriptomics to create a holistic understanding of biological systems. This shift will enable researchers to uncover deeper insights into physiological processes, complex regulations or disease mechanisms.
Another key trend will be the rise of spatial metabolomics and single-cell metabolomics. As more sensitive and faster instruments will be developed, the ability to analyze metabolic processes in a spatial 2D and 3D context, or even at the single-cell level, will become a reality. This will revolutionize our understanding of cellular dynamics and interplay.
For core facilities like the MCTP, these advancements imply a need for continuous investment in cutting-edge technologies, staff training as well as sustainable positions to handle increasingly complex workflows. Additionally, core facilities will likely play an even more critical role as hubs for collaborative research, facilitating the integration of metabolomics with other disciplines. Automation and AI-driven data analysis will also be essential for scaling up operations and maintaining the high throughput and quality that modern metabolomics demands. The challenge for core facilities will be to stay at the forefront of these technological shifts while ensuring accessibility for a broad range of users, from basic researchers to clinicians.
For researchers who are new to metabolomics, what advice would you give them when designing and conducting their experiments?
For researchers new to metabolomics, my key advice is to start with a well-defined question. Metabolomics is a powerful tool, but like any technique, it’s most effective when applied to specific, targeted hypotheses. Defining clear research objectives will help you choose the right experimental design, sample type, and analytical methods.
Secondly, sample preparation is critical in metabolomics as mentioned already. Small variations in how samples are collected, stored, or processed can significantly affect your results [e.g. Pre-analytical processing of plasma and serum samples for combined proteome and metabolome analysis]. Therefore, it’s important to standardize protocols as much as possible and pay close attention to quality control throughout the experiment.
Another key consideration is data analysis. Metabolomics can generate large and complex datasets, so it’s crucial to have a robust plan for data handling and interpretation before you start. Collaborating with bioinformaticians, statisticians or data scientists from the very beginning can be invaluable in ensuring your data is processed and analyzed correctly.
Finally, I would encourage new researchers to leverage the expertise of core facilities. Many facilities, like the MCTP, have advanced instruments and experienced staff who can provide guidance on experimental design, data acquisition, and analysis. This support can be especially helpful for those who are still building their experience in the field and that is why we always recommend to contact us as early as possible for project planning.
You are a member of the DGMet Working Group on Metabolomics Platforms, how do you see the role of core facilities and technology platforms in advancing the field of metabolomics and promoting best practices?
Core facilities and technology platforms play a crucial role in advancing many fields of high-end technologies, of course also metabolomics, and ensuring the adoption and development of best practices. As a member of the Working Group on Metabolomics Platforms of the German Society for Metabolomics, I have seen myself and heard from colleagues how these facilities act as central hubs for cutting-edge technology, expertise, and collaboration.
Core facilities provide access to advanced, expensive instrumentation, such as high-resolution mass spectrometry and automated sample preparation systems, that individual scientists may not have at their disposal, in particular early-career PIs and researchers. This makes access to top-tier analytical tools relatively easy and affordable, ensuring that researchers across disciplines and institutions can leverage metabolomics in their work, regardless of their own laboratory's resources.
Second, core labs are instrumental in promoting standardization and reproducibility. They often establish validated protocols for sample preparation and analysis, which helps to minimize variability and ensures that results are reliable and comparable across different studies. This is particularly important in a field like metabolomics, where small changes in methodology can lead to significant differences in the results.
Another important role of technology platforms is to foster collaboration. By serving as a centralized resource, they bring together scientists from different disciplines - such as biologists, chemists, and bioinformaticians - and facilitate multidisciplinary projects. This collaborative environment accelerates innovation and the development of new methodologies.
Finally, core labs often play an important role in training and education in their institutions, offering workshops, courses, and hands-on training that promote best practices across their own scientific community or even further. This helps ensure that researchers, especially those new to metabolomics, are well-equipped to design robust experiments and interpret their data accurately.
In summary, core labs and technology platforms not only can provide an infrastructure for high-quality metabolomics research but also play a pivotal role in fostering collaboration, and training the next generation of researchers.
