Associate Professor Stefan Arold has been with KAUST for a little over a year and has been busy building contacts…and building his lab, which is KAUST's first structural biology lab specializing in determining the atomic 3D structure of proteins and other biological macromolecules.

"It is very exciting, and a great opportunity, to be able to custom-build your own structural biology lab from scratch here in KAUST. However it was also very challenging—Firstly you have to choose and assemble all instruments and material as fast as possible. Choosing the big instruments such as the x-ray diffractometer or high-end biophysical tools was fun and rather easy. It's assembling the myriad of small things you need, which is difficult. Scales, tubes, filters, flasks, you name it. Often if you miss something small, then you won't be able to use those big machines," Arold said, when asked about what was involved in turning the previously empty space into a state-of-the-art research facility.

"Another great challenge was to continue producing scientific results while setting up our lab." Getting the lab up and running involved four to five months of planning and then the building phase began. But in the meantime, they were still able to continue their research.

"What allowed us to be productive even before our own lab was finished, was the Bioscience Core Lab at KAUST. It is equipped with the basic instruments and facilities we need to get our type of research going. The core lab is big enough so that the first members of my team could work in there while we were building up our own space. We didn't have to wait for our lab to be finished to do our research," Arold said. "I am also grateful for all the support I received from my colleagues, in terms of sharing their facilities, machines and KAUST-specific insights. Their warm welcome and collegiality really is key to our happiness here."

THE PROTEIN WORLD INSIDE US

Dr. Arold's research specialty is structural biology and molecular biophysics. He uses physical methods to study biological systems at a molecular level. More precisely, he uses an integrated 'hybrid' approach to analyze 3D structure and function of proteins. "Proteins are fascinating. They are life's molecular workhorses," Arold said. "In our body, they form nanoscale factories, railway systems, molecular portals and communication systems. It's their interactions with other proteins or other types of biomolecules that are at the heart of all biological functions. They are the basis for digestion, thinking, immune defense, anything really. But also for diseases, such as cancer, Alzheimer's, diabetes and so on. This nanoscale world that proteins and other biomolecules create is truly miraculous. We want to understand how proteins function to support life—and for this studying their 3D structure and interactions is essential."

GOING DEEP INTO RESEARCH

He says what makes his research different compared to most other methods used in biological sciences, is that his team has the capacity to understand how life works and functions at the atomic level.

"If you want to use a car to go shopping, for example, it may be enough to know that it has a motor and four wheels and how you drive it. But we want to know what exactly happens inside the motor when you hit the accelerator. This level of knowledge is needed if you want to understand the problems of the system and improve its performances," Arold explained. "In our research, we really want to understand on an atomic level how cells communicate and make decisions."

But he wants to take this in-depth understanding a step further and use it as an inspiration for engineering beneficial improvements on certain systems. "For instance, our collaboration with Dr. Heribert Hirt from the Center for Desert Agriculture may allow us to describe on a molecular level how plants sense and communicate a stress like drought or high salinity; this understanding could then inspire ways for improving their resistance," Arold said. "Similarly, our work within the CBRC [Center for Computational Bioscience] is expected to contribute to understanding and engineering microbes for microbial cell factories."

COLLABORATING FOR GREATER UNDERSTANDING

The research Dr. Arold's lab conducts is highly collaborative by nature. He describes what they do as "assembling the atomic pieces to understand the big puzzle."

"The principles of how structure, dynamics and interactions of proteins support biological function are of course the same in all life, including us, plants and bacteria," he explained. "Our work can add a deeper level of understanding, a greater resolution, if you wish, to almost all of bioscience. Together with the supportive structure and competence of my colleagues at KAUST, this creates great opportunities for innovative collaborations." Current examples include work with Dr. Mark Tester's team in KAUST's Salt Lab, aiming to construct a salt sensor. On the other side of the spectrum, his work with the groups of Dr. Vladimir Bajic and Dr. Xin Gao from the CBRC brings structural biology together with the latest machine learning algorithms to enable large-scale functional annotation of proteins.

THE BEGINNING OF NEW DISCOVERIES

Currently, Dr. Arold has eight people in his lab including three Ph.D. students, three post docs, one research scientist and one lab manager. Together they feature nine nationalities and speak nine languages. In this short time at KAUST, the collaborative work he and his team produced with colleagues from KAUST's BESE division and CBRC has already led to two publications, two more manuscripts are currently submitted and two more are in the final touches before submission. And with the new lab ready to go, we're sure more is soon to come.

By Michelle Ponto, KAUST News