A reflection of that trend can be found in the Federal University of Rio Grande do Sul (UFRGS) in Porto Alegre, in the far south of Brazil. Led by physicist Rita de Almeida, researchers in systems biology predict the behaviour of cells and organisms using theoretical models that treat the proteins, metabolites and other biomolecules in a given system as a complex, interactive network. Experimental data are crucial to validate the theoretical findings, which Almeida says is sourced from several large international databases in addition to an in-house cell culture laboratory.

Other groups in Brazil are exploiting interdisciplinary collaborations with biomedical and biological scientists. For example, a joint project with a pharmacologist proved vital in the development of a new imaging technique by Oscar de Mesquita and his team at the Federal University of Minas Gerais (UFMG) in Belo Horizonte. Like many physicists with a background in non-equilibrium dynamic systems, Mesquita was drawn towards biologically motivated research questions. "Biological materials are magnificent examples of non-equilibrium systems," he says.

The physicist was experimenting with ways to study the cellular process of phagocytosis – which allows cells to ingest nutrients and other particulate matter – with the eventual goal of exploiting the process for drug delivery. Peering through a defocussed microscope, he could make out half-micron-thick sections of cell membrane that would normally be invisible. This led to a new technique, defocusing microscopy, which has since been refined and used by researchers at UFMG to investigate cell behaviour and to study the properties of red blood cells.

Interdisciplinary collaboration is also thriving in experimental structural biology, a field that straddles the fine line between physics and biology. Richard Garratt at the IFSC is a biochemist by training, but has an intimate knowledge of the physical techniques that he uses, such as X-ray crystallography and nuclear magnetic resonance, to unlock the structural secrets of complex biological molecules and systems. "I don't feel out of place as a biochemist in a physics institute," he remarks.

Stand-out projects by Garratt's group have included fundamental investigations of septins, a group of filament-forming proteins that act as cellular scaffolds and diffusion barriers. X-ray crystallography enabled the researchers to solve the structures of several septins to an unprecedented resolution. "Our work has gained us a strong international reputation in this area of structural biology research," says Garratt. The group also helped develop a vaccine for the parasitic disease schistomiasis, which completed phase I clinical trials last year.

Garratt counts geneticists and immunologists among his collaborators, in addition to physicists who have migrated into the field. Andre Ambrosio of the Brazilian Biosciences National Laboratory (LNBio) in Campinas, and Garratt's former PhD student, is one such physicist. He runs an interdisciplinary group studying the metabolism of cancer with biologist colleague Sandra Dias.

In one major project, the researchers combined X-ray crystallography, protein biochemistry, biophysics and cancer cell models to examine how a group of proteins called glutaminases influence tumour metabolism. They discovered that one particular protein, Glutaminase C, plays a key role, and reported their findings in the Proceedings of the National Academies of Sciences last year. "This important glutaminase is now actively being investigated by drug companies," says Ambrosio.

While experimental research in biological physics is making a comeback, Brazilian researchers continue to produce quality theoretical work. Thadeu Penna of the Fluminense Federal University (UFF) in Niterói in the state of Rio de Janeiro is a computational physicist working on diverse applications of mathematical modelling. His most widely cited work is a simple computer model that accurately simulates the aging of a population, which has been widely adopted by the international research community. Penna himself is using the model to study the relationship between age and disease propagation, and between age and treatment success in tuberculosis and AIDS. "We are studying the aging-specific aspects of these diseases [to determine if] some ages are more responsive to treatment or more susceptible to infection," he explains.

Penna is largely positive about the transformation in Brazil's research environment over the last two decades. He describes being "dejected" with the physics community in Brazil after returning from a post-doc in the US in 1999. "Now, it has changed completely, in part due to the Brazilian government's efforts, but also due to state support agencies that have become more active in the past few years," he says. Garratt concurs, saying changes have been "universally positive", though he admits challenges remain. "We need to be advancing technologically, not just scientifically, we need in scientific terms to be improving quality and we still need to grow in terms of critical mass and infrastructure."

Medical applications drive industry

While scientists such as Almeida and Penna are attempting to understand the fundamentals of biological systems, physicists are also playing a crucial role in multidisciplinary medical research. One key success story has been biophotonics, in particular for dentistry applications. "Brazil is recognized worldwide in laser and light in dentistry, from basic to applied research as well as in clinical use," says Denise Zezell, of the Institute of Energy and Nuclear Research (IPEN) in São Paulo, which is also the country's leading centre for producing radiopharmaceuticals.

Zezell says that close collaboration with dentists, biochemists and other physicists has been instrumental in her research, which has included the the development of a clinically proven non-invasive laser technique that prevents tooth decay. Financial support provided by the state research foundation, FAPESP, in addition to government funding, has also been "decisive" in the success of her research.

Other key groups funded by FAPESP are two Research Centres in Optics and Photonics (CePOF), one at the IFSC and the other at the State University of Campinas. Photodynamic therapy for treating skin cancer is a central research theme at the IFSC, and its record on innovation is impressive. "We have about 14 products launched on the market together with Brazilian partner companies," says director Vanderlei Bagnato. "We also have about 12 spin-off companies and 5 national programmes that are developing and implementing new technologies."

But Oswaldo Baffa, a physicist at the University of São Paulo's Ribeirão Preto campus, says medical physics in the country is still young when it comes to clinical research, particularly in more traditional fields like radiation therapy. "At present we have a lot of research that is more academic-oriented," says Baffa. "Only recently people are starting to become aware of clinical-oriented research."

Baffa specializes in MRI, biomagnetism and clinical dosimetry, and is one of 12 physicists working in a multidisciplinary state-wide programme called CInAPCe that's using MRI to investigate epilepsy. "The idea was to improve the quality of our equipment in MRI and have a large number of subjects studied in the same equipment and conditions," says Baffa. The programme includes clinical and technical projects and already has "a wealth of data" that has been collected using state-of-the-art 3 T scanners across four institutions.

Brazil also has several research groups in the core medical physics discipline of radiation dosimetry. Successes at the Federal University of Pernambuco (UFPE) in Recife have included the CALDOSE_X software, which is now used in more than 40 countries to calculate the dose for diagnostic X-ray exposures. But perhaps a more valuable contribution is the development of new semiconductor detectors for quality assurance programmes in Brazilian hospitals. "This equipment is important for our country and the Latin America region because it is expensive to import equipment and maintain it," says group leader Helen Khoury.

Khoury points to a lack of funding for Brazilian companies as a primary factor preventing the transfer of her group's technology into industry. Baffa agrees, but is hopeful that the situation will improve with the first funding round for the medical, hospital and dental equipment arm of Sibratec – an innovation network set up by the federal funding agency FINEP to convert academic knowledge into industrial development – due to come on stream this year.

In broader terms, Baffa says serious challenges still remain, including shortages of medical physicists and a lack of professional regulation. "This is highly motivating and the necessary changes could be accomplished," he says. "I am optimistic for the future: for someone that has lived under high inflation and with economic uncertainties, the present situation with steady funding is a paradise."

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