Human Genome Project sequencing has provided the pieces of a complex jigsaw but working out how they interlock and what the completed picture represents is one of the challenges being tackled by University of Queensland researcher Dr Bostjan Kobe. His work is shedding light on the infection mechanisms of retroviruses such as HIV, human T-cell leukemia and Ebola.
Dr Kobe has received $80,000 in funding as part of the UQ Foundation Research Excellence Awards for this project entitled Structures of Retroviral Envelope Proteins and the Mechanism of Viral Infection.
"The knowledge of three-dimensional structures of proteins is essential for understanding their functions," said Dr Kobe.
"It is currently a very exciting time in structural biology, because the methods for the determination of three-dimensional structures are becoming more effective, and we can concentrate on trying to understand how the structure relates to function."
Dr Kobe's work in determining the three-dimensional structure of proteins insights into how those proteins function, how they affect biological processes and how therapeutic drugs can be designed.
A major part of the current work is looking at retroviruses such as HIV and Human T-cell leukemia (HTLV). Retroviruses must inject their genes into the interior of target cells so that they can replicate.
Determining the mechanism for retrovirus replication depends on understanding how the virus interacts with the target cell. The recent determination of the HTLV structure gives clues as to its method of infection and shows that it is very similar to the deadly Ebola virus.
The proposed model for infection shows how one protein anchors the virus to a target cell while another injects itself into the target cell membrane. The injected protein then changes shape to pull the virus hard up against the target cell and passes the virus genes into the target where they can replicate.
Gaining a better understanding of this mechanism will allow researchers to design techniques for halting the replication and spread of viruses such as HTLV and Ebola.
Another current project is tackling the problem of phenylketonuria, most familiar to people through warnings on the labels of soft-drinks and products containing some artificial sweeteners. Phenylketonuria is one of the first characterised genetic diseases and leads to mental retardation.
Sufferers of phenylketonuria and the less severe variant hyperphenylalaninemia, occur when an essential amino acid, levels of phenylalanine is not regulated properly.
"By working out the structure of the proteins involved in phenylalanine regulation, we have developed a better understanding of how genetic mutations lead to these diseases," says Dr Kobe.
"The results provide a set of simple rules that predict the severity of the phenylketonuria based on the protein structure. This sort of information is essential in finding treatments for the disease."
Dr Kobe holds a Wellcome Senior Research Fellowship in Medical Science for 1997-2002 and has been awarded the 2000 Erice Vaciago Award by the International School of Crystallography. For the period 1997-2002, Dr Kobe has been awarded over $1.9 million in research grants.
For more information contact Dr Bostjan Kobe on 3365 2132 or Peter McCutcheon at UQ Communications on 3365 1088, 0413 380012 or email communications@mailbox.uq.edu.au
