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 proetin sequences. Collaborators in this work include Kay Nieselt (Tübingen) and David Bryant (Otago).
- 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 am in the process of reviving 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. The direct biochemical and molecular biological evidence does not falsify the hypothesis. Experiments making use of recombinant, frame-shifted PrP species could have surprising results.
- Analysis of metabolomic data
Although there are very sophisticated techniques available for building large-scale kinetic models of metabolic processes, there are very few experimental data to which the methods can be applied. And the data are, by chemists' standards, very imprecise. Therefore there is a need for a common-sense, low-level empirical approach to determining what conclusions can actually be drawn about actual metabolic flows. An elementary approach to the analysis of time-series data is being developed and tested in collaboration with Silas Villas-Boas (Auckland) and Andreas Zell (Tübingen).
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
- Biophysical chemistry
Selected publications and creative works (Research Outputs)
- Carter, C. W., & Wills, P. R. (2017). Interdependence, reflexivity, fidelity, impedance matching, and the evolution of genetic coding. Molecular Biology and Evolution10.1093/molbev/msx265
- Wills, P. R., & Carter, C. W. (2017). Insuperable problems of the genetic code initially emerging in an RNA world. Bio Systems10.1016/j.biosystems.2017.09.006
- Wills, P. R., & Winzor, D. J. (2017). Rigorous analysis of static light scattering measurements on buffered protein solutions. Biophysical chemistry, 228, 108-113. 10.1016/j.bpc.2017.07.007
- Wills, P. R. (2016). A Hilly path through the thermodynamics and statistical mechanics of protein solutions. Biophysical Reviews, 8 (4), 291-298. 10.1007/s12551-016-0226-6
- Wills, P. R. (2016). The generation of meaningful information in molecular systems. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 374 (2063)10.1098/rsta.2015.0066
- Wills, P. R. (2016). DNA as information. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 374 (2063)10.1098/rsta.2015.0417
- Wills, P. R., Scott, D. J., & Winzor, D. J. (2015). The osmotic second virial coefficient for protein self-interaction: Use and misuse to describe thermodynamic nonideality. Analytical Biochemistry, 490, 55-65. 10.1016/j.ab.2015.08.020
- Wills, P. R., Nieselt, K., & McCaskill, J. S. (2015). Emergence of Coding and its Specificity as a Physico-Informatic Problem. Origins of Life and Evolution of Biospheres, 45 (1-2), 249-255. 10.1007/s11084-015-9434-5