Multidisciplinary functional genomics approaches to basic biological processes
The different approaches to functional genomics described (above and in this section) – gene expression and proteomics, structural genomics, comparative genomics and population genetics and bioinformatics – provide researchers with an extremely powerful multidisciplinary ‘toolbox’ which they can use to manipulate and study fundamental biological processes.
By picking the most appropriate genomic tools, or combination of these tools, for the job, researchers are developing innovative ways to study the basic structure and activity of molecular cell components and their interactions that enable organisms to function and reproduce over their lifetime. The multidisciplinary approach provides opportunities to look at these processes from different angles and gain new insights into the underlying workings of the cell.
The majority of diseases are caused when perfectly normal cellular processes malfunction, either because of external stimuli, such as pathogens or environmental factors, or because of inherited or acquired gene mutations resulting in incorrectly coded gene products unable to perform the role expected of them. In many common diseases, a combination of both genetic and environmental factors are responsible for cellular malfunction. By understanding normal cellular processes, in organisms as diverse as micro-organisms, plants and animals, researchers are better able to intervene with, or prevent, targeted cellular processes involved in disease. Two examples of these innovative research approaches are described below.
Inflammation
Inflammation is part of the body's natural defence system against injury and disease. On receipt of a specific chemical signal, certain cells such as leucocytes (white blood cells) ‘migrate’ towards the affected area to counter infection or repair damaged tissue. However, a malfunctioning of this system can cause cell migration to continue indefinitely, resulting in chronic inflammation – a major clinical problem implicated in many apparently unrelated disorders such as rheumatoid arthritis, asthma and skin disorders. In rheumatoid arthritis, for example, joint tissue is constantly destroyed by the migration of inflammatory cells, resulting in severe pain and reduced limb mobility.
By using a range of genomics tools to identify the signalling pathways and molecular networks involved in inflammatory cell migration towards and across injured tissues, and then testing these targets using in vitro and in vivo models supported by bioinformatics, researchers hope to explain the process of inflammatory cell migration and develop vital new drugs for chronic inflammatory conditions.
Epigenetics
Researchers are also using a multi-disciplinary functional genomics approach to explain the processes which ensure that not every gene making up our genome is expressed in every cell of our bodies. Brain cells, for example, do not make haemoglobin, the protein required to carry oxygen in blood, even though they – like all cells in the body – carry two copies of the gene which encodes the protein. Haemoglobin only needs to be produced in cells that differentiate into red blood cells. The regulatory processes which control which gene is turned on, or expressed, in each cell type determine that cell’s fate, i.e. whether it becomes a muscle cell, brain cell or liver cell, for example.
Genes unnecessary for a given cell's function are biochemically ‘tagged’ with methyl groups which can signal that the gene should be ‘silenced’ – a process called DNA methylation. Genes are silenced, or turned off, by tightly packing the DNA in that section of the genome in a DNA-protein complex called chromatin. Tightly compressed chromatin prevents RNA, the intermediary molecule necessary for gene expression, from getting to the DNA. If the chromatin is ‘open’, the genes can be switched on if required.
Processes such as DNA methylation, which alter the structure of the chromatin without changing the nucleotide sequence of the DNA, are known as epigenetic and considerably extend the information potential of the genetic code. DNA methylation is an essential process for normal cell development and functioning but can cause havoc in the body when it goes wrong. The uncontrolled cell division typical of most cancers, for example, can result from the abnormal epigenetic silencing of genes that control cell proliferation.
Epigenetic research is anticipated to have far-reaching implications for medicine. Using a combination of genomic tools, researchers are trying to better understand processes like DNA methylation so that they can use the information for more effective early diagnosis of cancer and to develop innovative treatments directly targeting the molecules involved in these processes.
Projects
Interated Projects
Mitocheck
FunGenES
Lymphangiogenomics
Network of Excellence
The Epigenome
MAIN: targeting cell migration in chronic inflammation
Streps
WOUND
Bacell Health
QUASI
Riboreg
Signalling & Traffic
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