Dr Oliver Rackham
My research experience has focused extensively on molecular interactions involving RNA and the development of new genetic systems to study them. For my doctoral research I studied RNA-protein interactions important to mRNA transport in mammalian cells, at the University of Otago, New Zealand. In 2003, I relocated to the MRC Laboratory of Molecular Biology, Cambridge University, UK, as an MRC Career Development Fellow. There I used directed evolution to re-engineer the protein synthesis machinery within the cell. My research at the WAIMR falls into two areas of interest: the biology of mammalian RNA-binding proteins, and synthetic biology using microbial model organisms.
Qualifications
| 1997 | BSc (Hons, first class) - Biochemistry, University of Otago, Dunedin, New Zealand |
| 2003 | PhD - Biochemistry, University of Otago, Dunedin, New Zealand
Thesis Title: "RNA-protein interactions in living cells" |
Research Interests
- Synthetic biology
- RNA-protein interactions
Current Research
Synthetic Biology
One of the key aims of synthetic biology is to program cells with new functions. To achieve this aim it will be necessary to create additional, new components that interact in a programmable manner, both with each other and with the existing cellular network. However, the activity of most cellular systems is constrained by their role in maintaining cell health. To escape this limitation, we use an "orthogonal" approach in which we build a parallel metabolism within the cell. To engineer components of this parallel metabolism we have created a powerful new genetic selection approach that can be used to tailor the molecular specificities of genes, RNAs and proteins in bacteria. In previous work we engineered a set of orthogonal ribosome-mRNA pairs as a proof of principle for this new approach. These pairs were used to create new gene regulatory modules in vivo, and in the large-scale identification of functionally important residues within the ribosome.
RNA-binding proteins
From synthesis to destruction, mRNAs are associated with an array of proteins. Proteins control the efficiency of transcription, processing, nuclear export, translation, localization and degradation of mRNA. The importance of regulation at the level of mRNA has become increasingly apparent with the discovery of disease causing defects in these processes. For instance, the absence of an RNA-binding protein, the fragile X mental retardation protein (FMRP), results in the most frequently inherited cause of mental retardation in humans. I have created a trimolecular fluorescence complementation technique that allowed the visualisation of RNA-protein interactions in living cells, for the first time. Using this method, we found that FMRP, a translational repressor, and IMP1, an RNA transport factor, formed a complex on common localised mRNAs; providing a hitherto unrecognised link between translation and localization in mammalian cells.
Scientific Involvement
- American Chemical Society - Member 2006 onwards.
- Australian Society for Biochemistry and Molecular Biology - Member 2006 onwards.
Major Grants Awarded
- ARC Discovery Project Grant [Sole CI]
- NHMRC Project Grant [CIB]
- NHMRC Peter Doherty Research Fellowship [Sole CI]
- Clive & Vera Ramaciotti Foundation Biomedical Research Grant [Sole CI]
- Medical Research Foundation Grant [Sole CI]
- Ada Bartholomew Medical Research Grant [Sole CI]
Top Publications
- Filipovska A, Rackham O. 2008. Building a parallel metabolism within the cell. ACS Chemical Biology 3(1):51-63.
[NCBI PubMed Entry]
- Rackham O, Wang K, Chin JW. 2006. Functional epitopes at the ribosome subunit interface. Nature Chemical Biology 2(5):254-8.
[NCBI PubMed Entry]
- Rackham O, Chin JW. 2006. Synthesizing cellular networks from evolved ribosome-mRNA pairs. Biochemical Society Transactions 34(Pt 2):328-9.
[NCBI PubMed Entry]
- Rackham O, Chin JW. 2005. Cellular logic with orthogonal ribosomes. Journal of the American Chemistry Society 127(50):17584-5.
[NCBI PubMed Entry]
- Rackham O, Chin JW. 2005. A network of orthogonal ribosome·mRNA pairs. Nature Chemical Biology 1(3):159-66.
[NCBI PubMed Entry]
- Rackham O, Brown CM. 2004. Visualization of RNA-protein interactions in living cells: FMRP and IMP1 interact on mRNAs. EMBO Journal 23(16):3346-55.
[NCBI PubMed Entry]
- Rackham O, Nichols SJ, Leedman PJ, Berners-Price SJ, Filipovska A. 2007. A gold(I) phosphine complex selectively induces apoptosis in breast cancer cells: implications for anticancer therapeutics targeted to mitochondria. Biochemical Pharmacology 74(7):992-1002.
[NCBI PubMed Entry]
- Jacobs GH, Rackham O, Stockwell PA, Tate WP, Brown CM. 2002. Transterm: a database of mRNAs and translational control elements. Nucleic Acids Research 30(1):310-1.
[NCBI PubMed Entry]
)