Victoria James
Research Fellow, Faculty of Medicine & Health Sciences
Contact
Teaching Summary
Gene Therapy Module, Foundation Year, BSc in Healthcare Science
Research Summary
MicroRNAs (miRNAs) are small (~21nt) RNAs which regulate gene expression by targeting messenger RNA (mRNA) and preventing translation. This central role means miRNAs are involved in all aspects of… read more
Recent Publications
JAMES, V, WONG, SCK and SHARP, T, 2012. MicroRNA-mediated gene silencing: Are we close to a unifying model. BioMolecular Concepts. (In Press.)
JAMES V*, FOXLER DE*, BRIDGE KS*, WEBB TM*, MEE M, WONG SCK, FENG Y, CONSTANTIN-THEODOSIU D, PETURSDOTTIR TE, BJORNSSON J, INGVARSSON S, RATCLIFFE PJ, LONGMORE GD and SHARP TV, 2012. The Limd1 Protein Bridges An Association Between The Prolyl Hydroxylases And Vhl To Repress Hif-1 Activity. Nature Cell Biology. 14(2), 201-8 GONZALEZ-ESTEVEZ C, FELIX DA, SMITH MD, PAPS J, MORLEY S, JAMES V, SHARP TV and ABOOBAKER A, 2012. SMG-1 and TORC1 act antagonistically to regulate response to injury and growth in planarians. PLoS Genetics. (In Press.)
FOXLER, DE, JAMES, V, SHELTON, SJ, VALLIM, TQD, SHAW, PE and SHARP, TV, 2011. Pu.1 Is A Major Transcriptional Activator Of The Tumour Suppressor Gene Limd1 Febs Letters. 585(7), 1089-1096
Current Research
MicroRNAs (miRNAs) are small (~21nt) RNAs which regulate gene expression by targeting messenger RNA (mRNA) and preventing translation. This central role means miRNAs are involved in all aspects of cellular homeostasis and have received considerable attention from the development and disease fields. Despite this importance the precise mechanism by which miRNAs regulate expression is not fully elucidated.
The classical action of miRNAs is to prevent translation of targeted mRNA, resulting in degradation of the majority of transcripts. However, not all targeted mRNAs are silenced in the same way; targeted mRNAs can be silenced then returned to translation, while others remain associated with ribosomes. These different outcomes can all be brought about by the same miRNA type (e.g. Let7), strongly implying the involvement of additional factors. These observations raise the question of how these same small RNAs can regulate such contradictory activities.
My research interests are in understanding the mechanisms that underlie the activity of miRNAs to regulate gene expression. In the hunt for additional regulatory factors, we recently identified the direct involvement of a tumour suppressor gene, LIM domain containing protein 1 (LIMD1), in miRNA mediated translational repression.
LIMD1 interacts with several components of the miRNA silencing machinery termed the RNA-Induced Silencing Complex (RISC). In addition, LIMD1 can also interact with key translation initiation factors e.g. eIF4E. We believe that it is this ability to interact with two discrete complexes, RISC and the translation initiation complex that allows LIMD1 to assist in mediating miRNA directed translation repression.
My research is now focussed on screening for additional regulatory factors like LIMD1 and understanding how variation/modification of RISC components leads to different mechanisms of silencing. Furthermore, I would like to pursue my findings in disease related models, particularly cancer, to determine how disruption/manipulation of this regulatory system contributes to disease.