At the left, Juan Carlos Martínez, beamline scientist at the NCD-SWEET beamline of the ALBA Synchrotron; Daniel Lucena and Juan Estévez, microtubule stabilizing agents group researchers at the Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC). At the right, Ana Joanquina Pérez-Berná, researcher of the MISTRAL beamline, during an experiment analysing cells infected by SARS-CoV-2.
Cerdanyola del Vallès, April 7, 2021.
Research in times of pandemic
The impact that the Covid-19 pandemic has had on research has been enormous, shifting efforts and adapting new lines of research, with the aim of better understanding how the virus works and finding new treatments or vaccines.
In April 2020, the ALBA Synchrotron opened a rapid access mode to enable carrying out experiments related to the SARS-CoV-2 virus. At the same time, and with the aim of not stopping science, remote analysis methods were optimized, especially in the beamline dedicated to macromolecular crystallography, and mail-in sample service was offered for recovering canceled experiments during the lockdown. By the end of 2020, 98% of the number of planned experiments had been performed, despite restrictions.
Synchrotron light against Covid-19
At ALBA, about 15 experiments have been carried out to study Covid-19 through both regular and rapid access mode. In addition, new experiments are yet to arrive from the last call for proposals, which ended in February 2021. The research groups involved come from both international and Spanish institutions.
Although most of them are academic users, it is worth mentioning that the first experiment on Covid-19 was that of an American industry that analyzed different ways to block the process of infection of SARS-CoV-2.
Most of the experiments linked to Covid-19 are in an analysis phase where results' dissemination is not possible yet. However, we can mention the work from the Margarita Salas Center for Biological Research (CIB-CSIC) that has studied, in the NCD-SWEET beamline, the possible effect of an antitumor drug for clinical use which acts on the life cycle of the SARS-CoV-2 coronavirus and interrupts transport and replication. It is also worth mentioning the study by Pablo Gastaminza, from the National Center for Biotechnology (CNB-CSIC), who in collaboration with the MISTRAL beamline researcher, Ana Joaquina Pérez-Berná, is currently analyzing three-dimensional images of cells infected by the virus. This information will open the door to new treatments for the disease. In the field of protein crystallography, different groups from the CSIC and other international institutions have used ALBA's facilities to solve the structure of several proteins related to Covid-19. Here you can see the news published by the ALBA Synchrotron about Covid-19.
Among the 8 operational beamlines, XALOC, MISTRAL and NCD-SWEET have hosted experiments related to the study of the virus. Each of them provides a unique way of using synchrotron light and analyzing data. XALOC, specialized in macromolecular crystallography, offers structural biology groups a tool to visualize with hard X-rays the structure of macromolecules and complexes. MISTRAL, equipped with a soft X-ray microscope, enables obtaining nano-CT-scans of biological material as well as spectroscopic and three-dimensional images of whole cells in conditions very close to their natural state. NCD-SWEET provides non-crystalline diffraction techniques that gives structural, dynamic, and organizational information on large molecular assemblages such as polymers, colloids, proteins, and fibers. It is a versatile tool for different research fields: medicine, biology, chemistry, physics, environment and materials science.
Dealing with other challenges in health
Apart from Covid-19, in 2020 the ALBA Synchrotron hosted many different experiments from other biomedical areas. As an example, advances have been made to understand how an optogenetic tool works, to understand how antitumor drug taxanes modulate microtubules in cells, and to assess tricine in cisplatin-based skin cancer treatment. A structural mechanism involved in bacterial conjugation was also discovered, images of how anticancer compounds move inside cells were obtained, or the anticoagulant potential of the tsetse fly to develop new drugs - also useful for patients with advanced symptoms of Covid-19 - was captured. Synchrotron light has also been key in the determination of the CCT protein in the control of the formation of the immune synapse, the development of a new method to visualize cells in a non-invasive way that reveals the structure of lipid droplets as well as to study muscular dystrophy. 30% of the total experiments carried out at the ALBA Synchrotron are devoted to the study of life sciences.
A decade of research at ALBA has contributed to the understanding of the molecular structure of coronaviruses and their mechanisms of infection in healthy cells. The upgrade project ALBA II will certainly be key in the field of health.
