Enabling technologies for manipulating multiple genes on complex pathways

Many complex biochemical pathways in plants have now been manipulated genetically, usually by suppression or over-expression of single genes. Further exploitation of the potential for plant genetic manipulation, both as a research tool and as a vehicle for plant biotechnology, will require the co-ordinate manipulation of multiple genes on a pathway. This goal is currently very difficult to achieve. A number of approaches have been taken to combine or 'pyramid' transgenes in one plant and have met with varying degrees of success. These approaches include sexual crossing, re-transformation, co-transformation and the use of linked transgenes. Novel, alternative 'enabling' technologies are also being developed that aim to use single transgenes to manipulate the expression of multiple genes. A chimeric transgene with linked partial gene sequences placed under the control of a single promoter can be used to co-ordinately suppress numerous plant endogenous genes. Constructs modelled on viral polyproteins can be used to simultaneously introduce multiple protein-coding genes into plant cells. In the course of our work on the lignin biosynthetic pathway, we have tested both conventional and novel methods for achieving co-ordinate suppression or over-expression of up to three plant lignin genes. In this article we review the literature concerning the manipulation of multiple genes in plants. We also report on our own experiences and results using different methods to perform directed manipulation of lignin biosynthesis in tobacco.</p

Inflammation and colorectal cancer

Chronic intestinal Inflammation occurs in response to environmental factors, infection and genetics; and plays a critical role in initiation, promotion, progression and metastasis of colon cancer. Colitis associated colon cancer (CAC) is a classic example of multifactorial, multi-step colorectal cancer associated with inflammatory bowel diseases. In recent years, the generation of animal models of CAC and recognition of the importance of the gut microbiota, altered immune system, and other environmental factors in CAC, has expanded the basic understanding of inflammation associated colon cancer. In this chapter, we discuss the cellular alterations and mechanisms by which inflammation contributes towards the development of colon cancer using CAC as a model system. We have also explored some of the promising strategies for preventing progression of inflammation to colon cancer. The emerging role of dietary factors, obesity and gut microbiota in colon cancer is also reviewed