Where physics meets life: biophysics and the future of innovation
On the point where principles of physics meet the complexity of biology lies the discipline of biophysics. By applying the methods and approaches of physics to biological processes, biophysics aims to find the physical processes that underlie the mechanisms of life.
Biophysical research leans strongly on the use of advanced technology, which means the field is positioned right at the cutting edge of science and technology. We talked with Valentina Zorzini, leader of the Biophysics Expertise Unit at the VIB-KU Leuven Center for Brain & Disease Research. We asked her about her passion for biophysics, the main goals and objectives for the unit, as well as how the newest equipment makes her unit one of the best in the world.
Hello Valentina! Could you tell me a bit more about the expertise unit you're running?
The Biophysics Expertise Unit – a technology platform run and established by the VIB-KU Leuven Center for Brain & Disease Research - is a state-of-the-art facility that runs an extended suite of experimental setups to produce proteins and measure protein folding, conformation, stability, and interaction with other biomolecules. We have seventeen instruments that cover three major pillars: structural characterization, biophysical characterization, and binding kinetics. The goal is to establish a pipeline that rapidly goes from protein production up to protein function characterization in a high-throughput manner . We are always exploring new technologies to make the unit more productive and efficient.
Could you briefly explain what biophysics is?
Biophysics is an interdisciplinary science that applies the methods and approaches of physics, biology, chemistry to study biological systems. All these subjects come together to help scientists understand the structure, dynamics, and function of living things at all levels, from molecules to organisms.
Biophysics, as a discipline, excels in the use of advanced instruments and in obtaining precise experimental parameters. But, it cannot independently address complex biological or biomedical questions. To fully interpret biophysical data, it must be complemented by approaches such as cell biology, molecular biology, or in vivo studies. While the biophysics unit can effectively address specific mechanistic questions, it is not enough on its own to provide a complete understanding of a biological system.
What made you fall in love with biophysics?
I fell in love with proteins during my studies, especially during my Master’s in Sweden, where I purified and characterized them. My passion grew even more during my PhD, trying to uncover the mysteries of life invisible to the naked eye, when I crystallized proteins and solved their atomic structures at high resolution.
Is there a role for AI in biophysics?
Yes, AI plays a significant and growing role in biophysics. AI could be of help to design or mutate proteins, but also to predict the 3D structure of proteins from their amino acid sequences. Then we can express and purify those proteins using, for example, one of the latest acquired instruments, the Nuclera e-protein platform. Once we obtain a good amount of purified protein, we can run biophysics, quality control, and interaction studies. AI can also analyze large datasets and make it automatic, as well as model complex systems such as neural networks or cellular interactions. It can also be integrated with liquid handling and dispensing robots, supported by control software.
What’s the toughest part of biophysics? And what’s the process of getting a sample analyzed?
The toughest part of biophysics often lies in the complexity and interdisciplinarity of the field. The integration of diverse knowledge, dealing with biological complexity, and managing multiscale systems makes biophysics particularly challenging but also incredibly exciting. In the day-to-day life in a biophysics lab, the hard work is maintaining seventeen instruments. But it is also a pleasure, because I get to switch between many different systems. The variety is fun, even if it can be demanding.
We start from prepared materials, for example, proteins. If a researcher brings a purified protein, we can run quality control: checking folding, conformation, and stability. We can also measure interactions with other proteins, compounds, small molecules, or peptides, for example.
If researchers don’t bring purified proteins, we can help synthesize and purify them. All of this can be done within 48-60 hours — from protein production to characterization. So, we cover the entire workflow from protein production to binding, biophysical, and structural characterization.
One of the advantages our unit has, is that we are exceptionally well-equipped with advanced instrumentation, allowing researchers to measure the same parameter using two, three, or even four different methods. So, we can conduct multiple, high-quality experiments in parallel or sequentially, often within a single day. With our state-of-the-art hardware, we are confident in stating that we are among the most advanced biophysics units in the world.
What are your goals for the future?
My goal is to establish a streamlined pipeline that seamlessly integrates protein production, characterization, and functional analysis with the ambitious aim of solving atomic structures in a high-throughput manner. By minimizing the consumption of proteins and ligands, this pipeline would enable researchers to complete all the steps from producing a protein to having the full analysis within days. Streamlining this workflow would significantly accelerate the entire process, allowing researchers to obtain comprehensive insights far faster than is currently possible.
There’s a lot of talk about innovation in science. Everything must be disruptive or groundbreaking. How do you see biophysics in the future revolutionizing brain research?
Establishing a fully integrated pipeline - from protein production and characterization to functional and interaction analysis within days - has the potential to be truly groundbreaking. Currently, the major bottleneck in many labs is obtaining high-quality proteins in sufficient quantities for downstream studies. By overcoming this hurdle, the pipeline will enable labs to accelerate their research significantly and increase overall productivity.
Importantly, this pipeline is versatile and can be applied across a wide range of projects, including those involving human samples and disease-related research. It is not restricted to any specific project type or sample origin, making it a valuable resource for diverse scientific endeavors.
As we continue to grow and acquire new instruments, we will keep enhancing our ability to address scientific questions from multiple angles. This in a way could really shape up the way we see biophysics, using it not just as a complement, but as a driving force to produce cutting edge neuroscience research. I see biophysics as a piece of a larger puzzle that will bring innovation to neuroscience research as we know it.
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