The Science - Professor Angus Lamond
PROTEOMICS SPLICING NUCLEOLUS SUBNUCLEAR BODIES…
Although the human genome has now been completely sequenced, we are still a long way from a full understanding of the proteins encoded by these genes and the complex biological systems in which they’re involved. A new fundamental concept called the “proteome” (i.e. the full set of proteins present) has recently emerged, and proteomics is a new discipline that complements genomic DNA research, by comparing the proteomes of cell structures and systems under different conditions to further unravel biological processes.
The process of gene expression in the cell is carried out by a series of “protein machines.” The process starts with DNA transcription (reading the “blueprint” for a protein on a particular gene) and carries through to production of that protein by ribosomes (“machines for making proteins”).
The production of a protein begins with a ribonucleic acid (RNA) copy of the DNA blueprint. The RNA cannot be translated into protein by the cells until certain stretches of information which are not required to make the protein are removed – literally “spliced” out of it.
RNA Splicing is performed by a protein machine termed the “spliceosome”, a complex of more than 50 proteins and small RNAs, acting together to catalyse this multi-step reaction. One of the Lamond group’s research goals is to shed further light on the organisation of this structure and its regulation within the cell nucleus. Until we understand how it functions normally, we cannot understand what has gone wrong in disease states which affect this particular cellular process.
The nucleolus is a subnuclear organelle (self-enclosed unit with a specific function) – the factory in which specific genes are transcribed, processed and assembled to form ribosome subunits.
Recent studies suggest that the mammalian nucleolus may also play roles in events leading to the development of tumours, as well as in viral replication and cellular stress sensing. However, the precise mechanisms involved still remain largely unknown.
The Lamond group studies the organisation of the cell nucleus, using fluorescently-tagged proteins and antibodies to “map” specific regions and structures. They also purify subcellular structures to identify as many of their protein components as possible (their ‘proteomes’), hence obtaining important clues to the functions of these structures within the cell. Nuclear bodies play important roles in controlling cell functions and are often altered or disrupted by stress, viral infection or cancer. Understanding nuclear bodies can thus help to understand and treat many forms of human disease.