Challenging project on cell structure attracts USD$1.5 million grant

Associate Professor Alex de Marco
Associate Professor Alex de Marco

Monash BDI scientist Associate Professor Alex de Marco is part of an international team that has gained a highly-competitive grant from the International Human Frontier Science Program Organization.

The Human Frontier Science Program Research Grant, worth USD$350,00 per year over three years, was awarded to Dr Oriol Gallego from Pompeu Fabra University, Barcelona, Spain (principal applicant), Associate Professor de Marco, and Dr Daniel Castano-Diez, University of Basel, Switzerland. Almost 550 teams applied for the grants with only 20 teams gaining one.

The program funds bold, cutting-edge projects by international teams that are not supported by more risk-averse funding bodies.

The grant will fund an ambitious study investigating the global mechanism controlling exocytosis using advanced imaging techniques. Exocytosis, by which biomolecules in cells are transported to the cell surface and secreted from its periphery, is an important process in cells.

The team is studying ‘constitutive exocytosis’, which is generally present in all eukaryotes where it regulates cell growth, cell progression and cell polarity. It is involved in multiple human pathologies including cancer and neurological disorders.

“What we are really trying to do is understand how the machineries that regulate constitutive exocytosis work together,” Associate Professor de Marco said. “The machineries are very complex and the process of exocytosis very dynamic,” he said.

No structural data about these collective machineries exists and although it has long been studied, the mechanism of exocytosis could not be reconstituted in vitro, he said.

The team combines the complementary expertise needed to equip it for the task from groups that are outstanding in their field: Dr Gallego is an expert in yeast biology and live cell imaging; Dr de Marco has expertise in developing methods for in-situ structural biology and instrumentation for high resolution cryo-EM imaging; and Dr Castano-Diez in developing computational analysis of cyro-EM data and software.

Using yeast cells, the multidisciplinary team will combine the use of live-cell imaging with the development of imaging instrumentation and advanced mathematical modelling to build an enhanced set-up capable of reconstructing the cellular machinery. Dr Gallego will develop molecular nano tools to allow the team to identify the parts of the process and hopefully see the event.

“It’s a very challenging project,” Associate Professor de Marco said. “We’ll develop new methods, based on cryogenic electron microscopy imaging to see how these complex machineries look like in a cell.

“If we were able to resolve this structure it would be a huge step forward,” he said.

“Exocytosis is one of the major processes in cells. Knowing how it actually works per se would be a very valuable set of information. We know this process is also very important in cancer and neurodegenerative disease so it could be very useful in drug development.”

The tools Dr de Marco is aiming to develop would also open doors for scientists working on a broad range of other work on cells.

The Human Frontier Science Program (HFSP) promotes international collaboration in basic research focused on the elucidation of the sophisticated and complex mechanisms of living organisms.

About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.