Associate Professor Peter Rowland Wills
BSc, PhD (Auckland)
Research | Current
- Origin of genetic coding
There is an enduring problem concerning the way in which information can gain meaning in material systems. The actual occurrence of one specific pattern (when many were originally possible) must become causally connected to a choice among some otherwise unrelated set of outcomes. Genes are nucleic acid sequences (linear patterns) that are causally connected, through sets of biochemical events, to the construction and maintenance of specific organisms. How did this connection arise? The synthesis of proteins with amino acid sequences that are accurately specified by nucleic acid sequences is the most obvious pathway whereby information stored in molecular systems finds meaning. The complicated process of ribosomal translation, the execution of the genetic code, is a primary mechanism whereby genetic information is expressed in functional form. My research focuses on the way in which the machinery necessary for the processes of genetic coding could have evolved through thermodynamically driven stages of self-organization which became progressively more complex, in terms of not only the biochemical machinery involved but also the computational steps necessary. This work ranges from what is broadly conceptual to what concerns itself with the fine details of protein sequences. My main collaborator in this area is Charlie Carter (Chapel Hill, North Carolina).
- Statistical thermodynamics of macromolecular solutions
Most studies of macromolecules in solution involve the measurement of quantities that are affected by thermodynamic non-ideality, but results are interpreted as if the solutions are ideal. Assessment of the effects of non-ideality on experimental results can lead to new information about molecular properties - size, shape, charge, etc. Theoretical work continues on the way in which accurate measurements using light-scattering, sedimentation, chromatographic and spectroscopic techniques can be correctly interpreted to help understand macromolecular interaction. This work is in collaboration with Don Winzor (Queensland).
Transmissible spongiform encephalopathy (TSE) continues to pose theoretical challenges, in spite of a wealth of data apparently demonstrating that the sole cause of disease is misfolding of the endogenous prion protein (PrP). I recently revived the hypothesis that prions induce the recoding of genetic information by affecting ribosomal frame-keeping and that the misfolding of prion proteins is by and large a byproduct of occasional frame-shifting during the synthesis of PrP. According to this hypothesis the destruction of cells in TSE originates in an avalanche of frame-shifting that destroys a cell’s capability to maintain a functional proteome rather than in the misfolding of otherwise normal proteins. Experiments making use of recombinant, frame-shifted PrP species have not yet reached the level of precision necessary to test the hypothesis conclusively, but my collaboration with Zoya Ignatova (Hamburg) continues.
Peter Wills began his scientific work in the field of physical biochemistry, studying applications of quasi-elastic light scattering to the investigation of macromolecules in solution. He then branched out into aspects of biophysical theory, especially the thermodynamics and statistical mechanics of macromolecular diffusion and sedimentation. This work was complemented with experimental investigations. His work in this area continues, mainly in collaboration with Prof. Don Winzor of the University of Queensland.
For about a decade, starting in the early 1980s, Peter Wills investigated theoretical aspects of diseases known as spongiform encephalopathies. Dr Carleton Gajdusek recognised him as an early advocate of the prion hypothesis and invited him to the US National Institutes of Health to pursue his studies there. The prion hypothesis now underpins the standard view of the aetiology of these diseases. He has recently revived the induced frameshifting hypothesis concerning prion replication.
Since working for a year in the laboratory of Manfred Eigen in Göttingen, Peter Wills has contributed to theories of the origin of life, especially the origin of genetic coding. Partly in collaboration with Dr Stuart Kauffman at the Santa Fe Institute, he has applied ideas about the accumulation of information in macromolecular systems to the study of autocatalytic networks. He has further extended these ideas to self organised systems in a critical state. His most recent collaborations are with Kay Nieselt in Tübingen, Peter Stadler in Leipzig and John McCaskill in Bochum. He is associated with both the MICREAgents and EVINCE consortia that are developing biomimetic electronic-chemical systems for nano-level unconventional computing.
Throughout his career Peter Wills has been a commentator on issues concerning the relationship of science and society. He was an active participant in debate about weapons of mass destruction during the Cold War and is now involved in discussions about pharmaceutical and agricultural applications of genetic engineering, especially its regulation. This work has often placed him in the midst of political dispute, including the discussion of matters concerning the Treaty of Waitangi.
Areas of expertise
- Biological self-organisation
- Origin of life
- aaRS enzymes
- Biophysical chemistry
Selected publications and creative works (Research Outputs)
- Carter, C. W., & Wills, P. R. (2019). Experimental solutions to problems defining the origin of codon-directed protein synthesis. Bio Systems, 18310.1016/j.biosystems.2019.103979
- Carter, C. W., & Wills, P. R. (2019). Class I and II aminoacyl-tRNA synthetase tRNA groove discrimination created the first synthetase-tRNA cognate pairs and was therefore essential to the origin of genetic coding. IUBMB life, 71 (8), 1088-1098. 10.1002/iub.2094
- Winzor, D. J., & Wills, P. R. (2019). Quantitative interpretation of isopiestic measurements on aqueous solutions: Urea revisited. Biophysical chemistry, 25110.1016/j.bpc.2019.106175
- Carter, C., & Wills, P. (2019). Class I and II aminoacyl-tRNA synthetase tRNA groove discrimination created the first synthetase•tRNA cognate pairs and was therefore essential to the origin of genetic coding. 10.1101/593269
- Czech, A., Konarev, P. V., Goebel, I., Svergun, D. I., Wills, P. R., & Ignatova, Z. (2019). Octa-repeat domain of the mammalian prion protein mRNA forms stable A-helical hairpin structure rather than G-quadruplexes. Scientific reports, 9 (1)10.1038/s41598-019-39213-2
- Carter, C. W., & Wills, P. R. (2018). Hierarchical groove discrimination by Class I and II aminoacyl-tRNA synthetases reveals a palimpsest of the operational RNA code in the tRNA acceptor-stem bases. Nucleic acids research, 46 (18), 9667-9683. 10.1093/nar/gky600
- Wills, P. R. (2018). Interactions between the prion protein and nucleic acids. Biochemistry and Biophysics Reports, 15, 68-68. 10.1016/j.bbrep.2018.07.004
- Wills, P. R. (2018). Lifes most distinguishing feature: meaningful information processing. Theoretical biology forum, 111 (1-2), 107-118. 10.19272/201811402013