Signalling To Telomeres: Mechanisms Of Action Of TGFb
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is contro ....Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is controlled by another protein called c-myc. This work will determine how telomerase is controlled by a balance between TGFb and c-myc in order to find ways to control telomerase and therefore cancer. We will use a combination of sophisticated techniques of cell molecular biology and biochemistry to pinpoint and target different molecules implicated in the actions of TGFb. This study will serve as an important baseline for more applied research in controlling ageing and cancer from development.Read moreRead less
Specificity Of Smad Proteins In Transforming Growth Factor-beta Signaling
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Transforming growth factor-betas (TGF-beta) regulate a fascinating array of cellular processes including cell proliferation, differentiation, migration, organization and death, as well as affect a wide range of biological functions, such as embryonic development, hematopoiesis and immune and inflammatory responses. Given the multifunctional nature of TGF-beta action, it is not surprising that the disruptions of TGF-beta functions have been implicated in many human disorders, particularly in colo ....Transforming growth factor-betas (TGF-beta) regulate a fascinating array of cellular processes including cell proliferation, differentiation, migration, organization and death, as well as affect a wide range of biological functions, such as embryonic development, hematopoiesis and immune and inflammatory responses. Given the multifunctional nature of TGF-beta action, it is not surprising that the disruptions of TGF-beta functions have been implicated in many human disorders, particularly in colorectal and pancreatic cancers. The Smad proteins (there are ten of them) are critical components of TGF-beta cellular actions. In fact, Smad4 also called DPC4 for deleted in pancreatic carcinoma locus 4. This project addresses how each Smad protein works at molecular level in the cell, and which part of biological functions it regulates. Collectively, the outcomes of the project may provide clear and specific molecular targets to treat TGF-beta related diseases such as colorectal and pancreatic cancers.Read moreRead less