From structural biology of neglected diseases to Brazilian science

This post was contributed by Dr Clare Sansom, of Birkbeck’s Department of Biological Sciences.

The prestigious Bernal Lecture is given annually at Birkbeck to honour the legacy of Professor J.D. Bernal, the first head of the Department of Crystallography (now part of Biological Sciences). In 2013 this lecture was given by a distinguished alumnus of the College, Professor Glaucius Oliva of the Institute of Physics of São Carlos, University of São Paulo, Brazil.  Introducing Professor Oliva, the Master of the College, Professor David Latchman, said that in the over forty years since the lecture series started, there had rarely been a better fit between Bernal’s interests in science and society and the chosen topic.

Professor Oliva spent four years at Birkbeck in the 1980s, studying for a PhD under Professor (now Sir) Tom Blundell. He started his lecture with a tribute to his colleagues from those days – many of whom were in the audience – mentioning in particular their passionate interest in their subject, hard work and desire that the knowledge they were gaining would be exploited for the good of society as a whole. His time in the Blundell lab at Birkbeck had, he said, changed his life. The main part of his lecture focused on two linked topics: the development of science in his native Brazil, and his research there into the structures of proteins that are linked to some of the world’s least studied infectious diseases.

There was very little science in Latin America until the early years of the twentieth century. Bernal described something of a “scientific renaissance” in the Spanish-speaking parts of the continent in his book The Social Function of Science (1939), but said very little there about Brazil. That country did, however, make its first serious investment in science and technology at about the same time, and continued to make slow progress throughout most of the last century, admittedly from a very low base. This growth has accelerated in the last decade, and the country now has a respectable place in the international tables: about 3% of all publications in peer reviewed journals include at least one Brazilian co-author. Even more encouragingly, there has been an enormous increase in enrolments into higher education since 2000. Significant challenges remain, however, particularly in encouraging private industry to invest in research and technology.  Brazil is a member of the increasingly influential BRIC group of large rapidly developing countries along with Russia, India and China, which, with other East Asian countries, is well ahead of the others in the group in patent numbers and similar metrics.

Links between the Department of Crystallography at Birkbeck and Brazil go back to the late 1970s and have made a significant contribution to the development of structural biology there. Professor Oliva was one of several young scientists to study here during the 1970s and 1980s. He returned to São Paulo in 1988 to set up his own crystallography lab. And he had to start small; his first major piece of equipment, an X-ray detector, arrived two years later.

Tackling infectious diseases
Since then, the research in Professor Oliva’s laboratory has focused on a group of infectious diseases that are common in tropical countries. Infectious diseases are still responsible for about a quarter of all deaths worldwide, and that proportion is far higher in low- and middle-income countries and in children. The effect of disease is often measured as a loss of “Disability Adjusted Life Years” (or DALYs) and these diseases, which are generally grouped together under the title of “neglected tropical diseases”, are estimated to cause about 90 million lost DALYs each year.

Professor Oliva described his group’s efforts to obtain information about the structures of proteins from the parasitic organisms that cause several of these diseases. Chagas’ disease is caused by a protozoan, Trypanosomacruzi, and is endemic in Central and South America. It is rarely fatal but chronic infection can cause debilitating and long-lasting disability. Professor Oliva’s group was the first to solve the structure of the enzyme glyceraldehyde-3-phosphatase from T. cruzi. This enzyme is essential for the parasite’s metabolism and its structure is distinctly different enough from that of the human enzyme for its inhibitors to show promise as anti-parasitic drugs. Developing such a drug, however, was always going to be difficult in a country with essentially no research pharmaceutical industry. The strategy pursued by Professor Oliva and his co-workers has been to exploit Brazil’s natural biodiversity, screening plant extracts against the structure to extract and purify compounds that are potent inhibitors of the enzyme. Some variants of the compounds originally identified in these screens are now undergoing pre-clinical testing as candidate drugs for Chagas’ disease. The group has also solved structures of an enzyme, purine nucleoside phosphorylase, from the parasitic flatworm Schistosomamansoni. This is one of the causative agents of schistosomiasis, a chronic, debilitating disease that can take a variety of forms; S. mansoni mainly causes hepatomegaly (enlarged liver) and other immune reactions.

Science without Borders
Professor Oliva returned to science policy towards the end of the lecture, in discussing the new Brazilian Science without Borders initiative, which he directs. This ambitious scheme aims to place at least 100,000 students and young scientists from Brazil in laboratories outside the country within four years.  Thanks to generous sponsorship – not least from the banking sector – 101,000 fellowships had been agreed and 41,000 awarded by May 2013.  So far, the UK is proving the second most popular destination country among Fellows appointed through this scheme. One of the first three to come to the UK, Dr.Jose Luiz Lopes from the University of São Paulo, spent a year working in Professor Bonnie Wallace’s lab in Biological Sciences. He is now back in Brazil as a postdoc, working in a collaborative project involving Birkbeck and the University of São Paulo that has joint financial support from BBSRC and Brazil’s CNPq. Birkbeck’s scientific links with Brazil are at least as strong as they were when Professor Oliva arrived here as a raw PhD student almost thirty years ago.


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