Sirius opens a window of opportunity for attracting research partnerships

Equipment will be used by several fields of science and propel the field of structural biology right from the start.

By Maria Fernanda Ziegler, in New York | Agência FAPESP – Two important developments for Brazilian research, which will be in operation next year, will provide a boost to research in structural biology, the branch of science that studies the structures of molecules involved in life, understanding how they relate to one another and to biological activities.

The rollout of the first stage of Sirius, the new Brazilian synchrotron light source and full operation of two cryo-electron microscopes – a cold technique that allows us to see the three-dimensional atomic structure of molecules – are expected to make scientific research more competitive.

"The coming year will be one of a lot of new developments, at least for us in the field of structural biology. In some aspects, we will enjoy financial gains. It will cost less to run our experiments. But the main thing will be gains in terms of competitiveness. It will be easier to train people and gain experience in order to compete with or contribute to global science," said Richard Charles Garratt, a professor at São Carlos Institute of Physics (IFSC) at the University of São Paulo (USP), during a presentation at FAPESP Week New York.

The meeting, held at the City University of New York (CUNY) November 26-28, 2018, involved Brazilian and U.S. researchers with the aim of strengthening research partnerships.

Garratt is referring to the window of opportunity for attracting international partnerships in scientific research using the synchrotron light. "Brazil has a window of opportunity because Sirius will be the most advanced in the world, at least for a little while, until other projects overtake it. This will attract scientists to collaboration with Brazilian researchers, which is always very positive," he said.

Septins

Garratt is responsible for the FAPESP-funded thematic project "Septins: comparative studies and the correlation between structure and function" designed to study the structural and functional aspects of septins (proteins that act in the final stage of cell division).

"They are more basic questions. Of course, the complexity of biology is incredible, and when any molecule stops functioning properly, the frequent result is a pathology linked to that functioning. Thus, it is no accident that septins are also found in some contexts of pathology, when they are being expressed in the wrong place or when there is a mutation, for example," he said.

Mutational defects or ectopic expression (gene expression in a location other than the normal) of septins had been associated with important pathologies such as male infertility, amyloidosis and cancer.

In recent years, the group led by Garratt has made contributions to the field of structural biology through the determination of the only high-resolution crystal structures of human septin domains, offering a wealth of information.

Synchrotron light

The new equipment is expected to give further impetus to the group’s work. "The first line of the Sirius light to be assembled is the protein crystallography line, which is the more traditional area within structural biology. In that line, we use the phenomenon of x-ray diffraction of crystals of the molecules we are interested in unraveling the structures of," said Garratt.

As a rule, to determine the position of each atom inside the molecule – the so-called three-dimensional structure of the molecule – we could use an x-ray beam (like the synchrotron light) on the molecule we are interested in. The light interacts with the material and is able to reveal characteristics about its molecular structure. By delivering the x-ray, we can measure patterns of dispersion determined by the position of the atoms in the molecule and thus gain an understanding.

"However, in practical terms, the problem is that the molecules are so small that the intensity of the dispersed beams would be very low. That is why, instead of examining a single molecule, it is more interesting to have a set of them. But they need to be arranged in the shape of a crystal. That is why studies in crystallography are important because they significantly simplify interpretation of the pattern," he said.

Cryo-electron microscopy

The two cryo-electron microscopes use another approach to the study of structural biology. The new method was also the highlight of the 2017 Nobel prize in chemistry. The prize was shared by Scottish structural biologist Richard Henderson, 72, from Cambridge University in the U.K., and biophysicists German-born Joachim Frank, 77, at Columbia University in New York, and Jacques Dubochet, 75, from the University of Lausanne, Switzerland.

"They were able to view the molecules directly instead of crystallizing the molecule they were interested in and then doing the experiment using x-rays. The final result is the same. That is the most recent technique. It is something that is taking the entire world by storm," he said.

FAPESP contributed to the purchase of the equipment that is now being installed in partnership with Brazilian Center for Research in Energy and Materials (CNPEM). "This will significantly change the way we do structural biology in Brazil because for the first time, we’ll have access to a tool able to do this work," he said.

Garratt explains that many systems, as is the case with septins, are extremely difficult to crystallize. "We need to make simplifications to get to the crystals, and by simplifying the system, we lose information. We will take a step forward using the cryo-electron microscope," he said.