John McCaskill

Last updated

John McCaskill
John McCaskill.jpg
Born1957
Australia
Alma mater University of Sydney
OccupationChemist
Known forInformation processing in evolving and self-organizing molecular systems

John S. McCaskill (born 1957) is an Australian chemist who works in a wide variety of fields ranging from theoretical biochemistry to novel computation to artificial life.

Contents

Biography

After graduating from Sydney University in 1978 (R. G. Gilbert advisor) and obtaining his PhD (D. Phil.) in 1982 as a Rhodes Scholar at New College, Oxford, McCaskill joined the group of Nobel prize-winner Manfred Eigen at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany. He became Professor for Theoretical Biochemistry at the Friedrich Schiller University Jena in 1992, founding a multidisciplinary research group in Biomolecular Information Processing (BioMIP) at the Institute for Molecular Biotechnology (imb Jena), a field which he pioneered for 25 years while holding positions at the GMD (National Research Center for Information Technology), the Fraunhofer Society, Ruhr University Bochum, the Santa Fe Institute, and the European Centre for Living Technology at the Ca' Foscari University of Venice. [1]

Research

McCaskill is best known for his work on information processing in evolving and self-organizing molecular systems, spanning theoretical and experimental approaches that include novel devices and systems. His early work on molecular evolution was theoretical, using non-equilibrium statistical mechanics to solve Eigen’s equations of molecular quasispecies for realistic fitness landscapes [2] . [3] He developed an ensemble approach to RNA structure prediction, now in wide use, [4] and made several contributions, both theoretical and experimental, to the study of spatially-resolved molecular evolution, including the experimental implementation of spatially-resolved capillary and microfluidic flow reactors [5] [6] and also including the construction of NGEN and MEREGEN, large-scale reconfigurable systolic computers for simulating spatial evolution based on reprogrammmable FPGA hardware [7]

Since 2000, he has established a chemical microprocessor technology for electronically programmable matter via microscale electrochemistry, and applied it to the development of novel approaches towards artificial cells and DNA/RNA processing systems, including in vitro DNA/RNA processing systems, including Qß RNA, 3SR, SDA, 3SR-Predator-Prey , [8] CATCH [9] and optical DNA Computing systems based on magnetic beads in microfluidic reactors [10] McCaskill led an international initiative to investigate evolvable artificial chemical cells with an EU-funded project, PACE, one of the earliest projects to explore a bottom-up approach to create an artificial living cell [11] [12] [13] . [14] Most recently his research has led to the development of novel autonomous and programmable electronic-chemical systems, leading other EU-funded projects, ECCell and MICREAgents, and opening a wide range of potential applications in basic and applied research.

McCaskill's current work includes modeling the essential interplay of self-organization and evolution in life-like chemical systems, and exploring the potential of electronic-chemical hybrid Information Technology based on these properties. He has produced over 100 scientific publications, taught courses and supervised PhD theses in disciplines ranging from chemistry, physics and biology to computer science, and his multidisciplinary work straddling theory and experiment has been recognized in invited lectures at international conferences around the world. He was an inaugural director of the European Centre for Living Technology, and has since served on its science board. While McCaskill's main work is in basic science, it has helped spawn several start-up companies and continues to involve the coordination of major collaborative projects fostering novel links between science and industry.

Related Research Articles

The quasispecies model is a description of the process of the Darwinian evolution of certain self-replicating entities within the framework of physical chemistry. A quasispecies is a large group or "cloud" of related genotypes that exist in an environment of high mutation rate, where a large fraction of offspring are expected to contain one or more mutations relative to the parent. This is in contrast to a species, which from an evolutionary perspective is a more-or-less stable single genotype, most of the offspring of which will be genetically accurate copies.

<span class="mw-page-title-main">RNA world</span> Hypothetical stage in the early evolutionary history of life on Earth

The RNA world is a hypothetical stage in the evolutionary history of life on Earth, in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. The term also refers to the hypothesis that posits the existence of this stage.

<span class="mw-page-title-main">Library (biology)</span> Collection of genetic material fragments

In molecular biology, a library is a collection of genetic material fragments that are stored and propagated in a population of microbes through the process of molecular cloning. There are different types of DNA libraries, including cDNA libraries, genomic libraries and randomized mutant libraries. DNA library technology is a mainstay of current molecular biology, genetic engineering, and protein engineering, and the applications of these libraries depend on the source of the original DNA fragments. There are differences in the cloning vectors and techniques used in library preparation, but in general each DNA fragment is uniquely inserted into a cloning vector and the pool of recombinant DNA molecules is then transferred into a population of bacteria or yeast such that each organism contains on average one construct. As the population of organisms is grown in culture, the DNA molecules contained within them are copied and propagated.

Xenobiology (XB) is a subfield of synthetic biology, the study of synthesizing and manipulating biological devices and systems. The name "xenobiology" derives from the Greek word xenos, which means "stranger, alien". Xenobiology is a form of biology that is not (yet) familiar to science and is not found in nature. In practice, it describes novel biological systems and biochemistries that differ from the canonical DNA–RNA-20 amino acid system. For example, instead of DNA or RNA, XB explores nucleic acid analogues, termed xeno nucleic acid (XNA) as information carriers. It also focuses on an expanded genetic code and the incorporation of non-proteinogenic amino acids, or “xeno amino acids” into proteins.

<span class="mw-page-title-main">Chemical biology</span> Scientific discipline

Chemical biology is a scientific discipline between the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and manipulation of biological systems. Although often confused with biochemistry, which studies the chemistry of biomolecules and regulation of biochemical pathways within and between cells, chemical biology remains distinct by focusing on the application of chemical tools to address biological questions.

Deoxyribozymes, also called DNA enzymes, DNAzymes, or catalytic DNA, are DNA oligonucleotides that are capable of performing a specific chemical reaction, often but not always catalytic. This is similar to the action of other biological enzymes, such as proteins or ribozymes . However, in contrast to the abundance of protein enzymes in biological systems and the discovery of biological ribozymes in the 1980s, there is only little evidence for naturally occurring deoxyribozymes. Deoxyribozymes should not be confused with DNA aptamers which are oligonucleotides that selectively bind a target ligand, but do not catalyze a subsequent chemical reaction.

<span class="mw-page-title-main">Aptamer</span> Oligonucleotide or peptide molecules that bind specific targets

Aptamers are short sequences of artificial DNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules. They exhibit a range of affinities, with variable levels of off-target binding and are sometimes classified as chemical antibodies. Aptamers and antibodies can be used in many of the same applications, but the nucleic acid-based structure of aptamers, which are mostly oligonucleotides, is very different from the amino acid-based structure of antibodies, which are proteins. This difference can make aptamers a better choice than antibodies for some purposes.

Threose nucleic acid (TNA) is an artificial genetic polymer in which the natural five-carbon ribose sugar found in RNA has been replaced by an unnatural four-carbon threose sugar. Invented by Albert Eschenmoser as part of his quest to explore the chemical etiology of RNA, TNA has become an important synthetic genetic polymer (XNA) due to its ability to efficiently base pair with complementary sequences of DNA and RNA. The main difference between TNA and DNA/RNA is their backbones. DNA and RNA have their phosphate backbones attached to the 5' carbon of the deoxyribose or ribose sugar ring, respectively. TNA, on the other hand, has it's phosphate backbone directly attached to the 3' carbon in the ring, since it does not have a 5' carbon. This modified backbone makes TNA, unlike DNA and RNA, completely refractory to nuclease digestion, making it a promising nucleic acid analog for therapeutic and diagnostic applications.

An artificial cell, synthetic cell or minimal cell is an engineered particle that mimics one or many functions of a biological cell. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such, liposomes, polymersomes, nanoparticles, microcapsules and a number of other particles can qualify as artificial cells.

Steven Albert Benner is an American chemist. He has been a professor at Harvard University, ETH Zurich, and most recently at the University of Florida, where he was the V.T. & Louise Jackson Distinguished Professor of Chemistry. In 2005, he founded The Westheimer Institute of Science and Technology (TWIST) and the Foundation For Applied Molecular Evolution. Benner has also founded the companies EraGen Biosciences and Firebird BioMolecular Sciences LLC.

A viral quasispecies is a population structure of viruses with a large number of variant genomes. Quasispecies result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds.

<span class="mw-page-title-main">Molecular biophysics</span> Interdisciplinary research area

Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms of molecular structure, structural organization, and dynamic behaviour at various levels of complexity. This discipline covers topics such as the measurement of molecular forces, molecular associations, allosteric interactions, Brownian motion, and cable theory. Additional areas of study can be found on Outline of Biophysics. The discipline has required development of specialized equipment and procedures capable of imaging and manipulating minute living structures, as well as novel experimental approaches.

mRNA display

mRNA display is a display technique used for in vitro protein, and/or peptide evolution to create molecules that can bind to a desired target. The process results in translated peptides or proteins that are associated with their mRNA progenitor via a puromycin linkage. The complex then binds to an immobilized target in a selection step. The mRNA-protein fusions that bind well are then reverse transcribed to cDNA and their sequence amplified via a polymerase chain reaction. The result is a nucleotide sequence that encodes a peptide with high affinity for the molecule of interest.

<span class="mw-page-title-main">Systematic evolution of ligands by exponential enrichment</span> Technique for producing oligonucleotides that specifically bind to a target

Systematic evolution of ligands by exponential enrichment (SELEX), also referred to as in vitro selection or in vitro evolution, is a combinatorial chemistry technique in molecular biology for producing oligonucleotides of either single-stranded DNA or RNA that specifically bind to a target ligand or ligands. These single-stranded DNA or RNA are commonly referred to as aptamers. Although SELEX has emerged as the most commonly used name for the procedure, some researchers have referred to it as SAAB and CASTing SELEX was first introduced in 1990. In 2015, a special issue was published in the Journal of Molecular Evolution in the honor of quarter century of the discovery of SELEX.

In vitro compartmentalization (IVC) is an emulsion-based technology that generates cell-like compartments in vitro. These compartments are designed such that each contains no more than one gene. When the gene is transcribed and/or translated, its products become 'trapped' with the encoding gene inside the compartment. By coupling the genotype (DNA) and phenotype, compartmentalization allows the selection and evolution of phenotype.

<span class="mw-page-title-main">Chemoton</span> Abstract model for the fundamental unit of life

The term chemoton refers to an abstract model for the fundamental unit of life introduced by Hungarian theoretical biologist Tibor Gánti. Gánti conceived the basic idea in 1952 and formulated the concept in 1971 in his book The Principles of Life. He suggested that the chemoton was the original ancestor of all organisms.

<span class="mw-page-title-main">Hypercycle (chemistry)</span> Cyclic sequence of self-reproducing single cycles

In chemistry, a hypercycle is an abstract model of organization of self-replicating molecules connected in a cyclic, autocatalytic manner. It was introduced in an ordinary differential equation (ODE) form by the Nobel Prize in Chemistry winner Manfred Eigen in 1971 and subsequently further extended in collaboration with Peter Schuster. It was proposed as a solution to the error threshold problem encountered during modelling of replicative molecules that hypothetically existed on the primordial Earth. As such, it explained how life on Earth could have begun using only relatively short genetic sequences, which in theory were too short to store all essential information. The hypercycle is a special case of the replicator equation. The most important properties of hypercycles are autocatalytic growth competition between cycles, once-for-ever selective behaviour, utilization of small selective advantage, rapid evolvability, increased information capacity, and selection against parasitic branches.

<span class="mw-page-title-main">Xeno nucleic acid</span> Synthetic nucleic acid analogues

Xeno nucleic acids (XNA) are synthetic nucleic acid analogues that have a different backbone from the ribose and deoxyribose found in the nucleic acids of naturally occurring RNA and DNA.

<span class="mw-page-title-main">Nils G. Walter</span> Professor of Chemistry, Biophysics, and Biological Chemistry

Nils G. Walter, Dr. Ing., is the Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry at the University of Michigan, Ann Arbor. Research in the Nils Walter Lab focuses on non-coding RNA through the lens of single molecule techniques. He is the Founding Director of the Single Molecule Analysis in real-Time (SMART) Center at Michigan. In addition, Walter is the Founding Co-Director for the University of Michigan Center for RNA Biomedicine whose mission is to enrich the university’s intellectual and training environment around RNA Biomedicine. He is currently an Associate Director for the Michigan Post-baccalaureate Research Education Program (PREP).

Living technology is the field of technology that derives its functionality and usefulness from the properties that make natural organisms alive. It may be seen as a technological subfield of both artificial life and complex systems and is relevant beyond biotechnology to nanotechnology, information technology, artificial intelligence, environmental technology and socioeconomic technology for managing human society.

References

  1. John, McCaskill. "McCaskill CV" (PDF). biomip.org. Retrieved 7 August 2019.
  2. McCaskill, J. S. (1984). "A localization threshold for macromolecular quasispecies from continuously distributed replication rates". The Journal of Chemical Physics. 80 (10): 5194–5202. Bibcode:1984JChPh..80.5194M. doi:10.1063/1.446590.
  3. Eigen, Manfred, McCaskill, John, and Schuster, Peter. "The molecular quasi-species." Adv. Chem. Phys 75 (1989): 149-263, 1988. doi:10.1002/9780470141243.ch4
  4. McCaskill, John (1990). "The equilibrium partition function and base pair binding probabilities for RNA secondary structure". Biopolymers. 29 (6–7): 1105–1119. doi:10.1002/bip.360290621. hdl: 11858/00-001M-0000-0013-0DE3-9 . PMID   1695107. S2CID   12629688.
  5. McCaskill, J.S.; Bauer, G.J. (1993). "Images of evolution: origin of spontaneous RNA replication waves". Proc. Natl. Acad. Sci. USA. 90 (9): 4191–4195. Bibcode:1993PNAS...90.4191M. doi: 10.1073/pnas.90.9.4191 . PMC   46472 . PMID   7683426.
  6. McCaskill, John (1997). "Spatially resolved in vitro molecular ecology". Biophysical Chemistry. 66 (2–3): 145–158. doi:10.1016/s0301-4622(97)00073-2. PMID   9362557.
  7. Tangen, U., Maeke, Th and McCaskill, J.S. "Advanced simulation in the configurable massively parallel hardware MereGen." Coupling of Biological and Electronic Systems. Springer, Berlin, Heidelberg, 2002. 107-118.
  8. Wlotzka, Britta; McCaskill, John (1996). "A molecular predator and its prey: coupled isothermal amplification of nucleic acids" (PDF). Chemistry and Biology. 4 (25–33): 25–33. doi: 10.1016/s1074-5521(97)90234-9 . PMID   9070425 . Retrieved 13 August 2019.
  9. Ellinger, Thomas; Ehricht, Ralf; McCaskill, John (1998). "In vitro evolution of molecular cooperation in CATCH, a cooperatively coupled amplification system". Cell Chemical Biology. 5 (12): 729–241. doi: 10.1016/s1074-5521(98)90665-2 . PMID   9862794.
  10. McCaskill, John (2001). "Optically programming DNA computing in microflow reactors". Bio Systems. 59 (2): 125–138. Bibcode:2001BiSys..59..125M. doi:10.1016/s0303-2647(01)00099-5. PMID   11267740.
  11. "Holy Grail of Artificial Life". The Irish Times. 2 September 2004.
  12. "The God-Machine. Is life to be created anew? (Die Gottes-Maschine. Ist das Leben ganz neu zu erfinden?)". GEO. August 2009.
  13. Lütke-Wissing, Stefan. "Die geheimen Baupläne der Natur". TIB Leibniz-Informationszentrum. Retrieved 13 August 2019.
  14. Regis, Ed (2008). What is Life?. New York: Farrar, Straus and Giroux. pp. 140–141. ISBN   978-0-374-28851-8.