Associate Professor Oliver Rackham
Associate Professor Rackham gained his Bachelor of Science and Doctorate in Biochemistry at the University of Otago, Dunedin, New Zealand. In 2003 Oliver relocated to the MRC Laboratory of Molecular Biology, UK, as an MRC Career Development Fellow, working with Professor Jason Chin on approaches to systematically re-engineer the genetic code.
Oliver established his own group at the Perkins in 2006 as an NHMRC Peter Doherty Fellow. Since then he has been awarded a Wenner-Gren Foundation Fellowship, an ARC Future Fellowship, the Marshall Medal, and was admitted to the European Inventor Hall of Fame. Oliver’s research is currently funded by grants from the ARC and NHMRC.
Associate Professor Rackham‘s research falls into two areas of interest: engineering and understanding mammalian gene expression, and synthetic biology using microbial model organisms. His work focuses on developing new tools and therapeutics to target cancer, mitochondrial diseases and antibiotic-resistant bacteria.
One of the key aims of synthetic biology is to program cells with new functions. To achieve this aim it is necessary to create additional, new components that interact in a programmable manner, both with each other and with the existing cellular network. To engineer these components we have created a number of powerful new genetic selection approaches that can be used to tailor the molecular specificities of genes, RNAs and proteins in bacteria and yeast. Current projects involve manipulating bacteria to efficiently express proteins containing selenium and engineering yeast to produce new antibiotics.
Mammalian Gene Expression
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. We are using synthetic biology and transcriptomic approaches to engineer and understand mammalian RNA-binding proteins for use as tools in biotechnology and as therapeutics for human diseases.
- Kummer E, Leibundgut MA, Rackham O, Lee RG, Boehringer D, Filipovska A, Ban N. (2018) Unique features of mitochondrial translation initiation revealed by cryo-EM. Nature 560:263-267.
- Spåhr H, Chia T, Lingford JP, Siira SJ, Cohen SB, Filipovska A, Rackham O. (2018) Modular ssDNA binding and inhibition of telomerase activity by designer PPR proteins. Nature Communications 9(1):2212.
- Scott LH, Mathews JC, Flematti GR, Filipovska A, Rackham O. (2018) An artificial yeast genetic circuit enables deep mutational scanning of an antimicrobial resistance protein. ACS Synthetic Biology 7(8):1907-1917.
- Wallis CP, Filipovska A, Rackham O. (2018) Tighter ligand binding can compensate for impaired stability of an RNA-binding protein. ACS Chemical Biology 13(6):1499-1505.
- Wallis CP, Filipovska A, Rackham O. (2018) A modified yeast three-hybrid system enabling both positive and negative selections. Biotechnology Letters 40(7):1127-1134.
- Siira S, Spåhr H, Shearwood AJ, Ruzzenente B, Larsson NG, Rackham O, Filipovska A. (2017) LRPPRC-mediated folding of the mitochondrial transcriptome. Nature Communications 8(1):1532.
- Kuznetsova I, Siira SJ, Shearwood AJ, Ermer JA, Filipovska A, Rackham O. (2017) Simultaneous processing and degradation of mitochondrial RNAs revealed by circularized RNA sequencing. Nucleic Acids Research 45(9):5487-5500.
- Rackham O, Busch JD, Matic S, Siira S, Kuznetsova I, Atanassov I, Ermer JA, Shearwood AJ, Richman TR, Stewart J, Mourier A, Milenkovic D, Larsson NG, Filipovska A. (2016) Hierarchical RNA processing is rate limiting for mitochondrial ribosome assembly. Cell Reports 16(7):1874-90.
- Coquille S, Filipovska A, Chia T, Rajappa L, Lingford JP, Razif MF, Thore S, Rackham O. (2014) An artificial PPR scaffold for programmable RNA recognition. Nature Communications 5:5729.
- Filipovska A, Rackham O. (2013) Specialization from synthesis: how ribosome diversity can customize protein function. FEBS Letters 587(8):1189-1197.
- Thyer R, Filipovska A, Rackham O. (2013) Engineered rRNA enhances the efficiency of selenocysteine incorporation during translation. Journal of the American Chemical Society (JACS) 135(1):2-5.
- Filipovska A, Rackham O. (2012) Modular recognition of nucleic acids by PUF, TALE and PPR proteins. Molecular Biosystems 8(3):699-708.
- Rackham O, Shearwood AM, Mercer TR, Davies SM, Mattick JS, Filipovska A. (2011) Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA 17(12):2085-93.
- Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, Haugen E, Bracken CP, Rackham O, Stamatoyannopoulos JA, Filipovska A, Mattick JS. (2011) The human mitochondrial transcriptome. Cell 146(4):645-58.
- Filipovska A, Razif MF, Nygård KK, Rackham O. (2011) A universal code for RNA recognition by PUF proteins. Nature Chemical Biology 7(7):425-427.
- Filipovska A and Rackham O. (2008) Building a parallel metabolism within the cell. ACS Chemical Biology 3(1):51-63.
- Rackham O, Wang K, Chin JW. (2006) Functional epitopes at the ribosome subunit interface. Nature Chemical Biology 2(5):254-258.
- Rackham O, Chin JW. (2005) Cellular logic with orthogonal ribosomes. Journal of the American Chemical Society (JACS) 127(50):17584-17585.
- Rackham O, Chin JW. (2005) A network of orthogonal ribosome•mRNA pairs. Nature Chemical Biology 1(3):159-166.
- Rackham O, Brown CM. (2004) Visualization of RNA-protein interactions in living cells: FMRP and IMP1 interact on mRNAs. EMBO Journal 23(16):3346-3355.