In silico Platforms
Kunjulakshmi R
BS-MS Third Year, Biological Sciences
The 21st century has seen remarkable feats. Sending spacecraft to the peripheral reaches of the solar system, scouting the Higgs boson, or even editing DNA to test reproductive boundaries. We might have overlooked a key advancement that has made research, particularly in biological sciences feel like a waltz. Conducting experiments ONLY using a computer.
The basic idea behind Synthetic Biology is reconstruction from parts and this is what it makes different from normal Biology in which we focus on studying and analysing the parts rather than reconstructing them.
The concepts of synthetic biology starting from design and creation of parts, formulating rules and models and finally standardizing the genome, is replete with computational principles at most stages. The resources used for these are often termed as “in silico platforms”. The term “in silico” - a Pseudo-Latin word for “in silicon” was coined in 1987 by Christopher Langton to describe artificial life. But the first biological experiment carried out “in silico” was in 1989 by a mathematician. Crafting synthetic gene circuits requires the proposal of models including mechanistic or statistical or both. Statistical models provide mathematical expression to the observed data while mechanistic models provide mathematical expression to the underlying biological processes. Frequently, computational work relies more on statistical models.
DNA construction bricks (genes, translational initiation regions, promoters etc.) as well as protein parts (structural proteins, regulators, sensory proteins etc.) are the workhorses of any Synbio based research. These parts are precisely induced with changes at a computer interface. For example, in studying the process of making a protein from RNA, or translation, computational algorithms can be used to propose a thermodynamic model or a kinetic model for translational initiation by simulating the interactions crucial to the process. Thermodynamic models help in understanding the system behaviour and in determining the properties such as enthalpy, phase equilibrium etc. (If we consider the initiation of translation, equilibrium constants for the interaction between 5’ cap and the eukaryotic initiation factors (eIF) should be in the range of 279-314K and these conditions are predicted by the thermodynamic model). On coming to the kinetic model, we are mainly interested in giving mathematical descriptions for each reaction step as a function of components of the system. These computational approaches revolve around taking some data as inputs, processing them through methods that can mimic the biological environment in some sense and predicting outcomes of the process we are interested in. There are also computational approaches at the level of transcription which modulate the formation of messenger RNA by reading the genetic sequences.
Computer aided design tools are also required for data exchange standards, tools for specifying and composing systems, for the workflow of systems. “Compilers” are used for translating for simulating and analysing the behaviour of gene circuits at various levels of resolution.
One of the main research activities in synthetic biology – DNA synthesis and genome designing – exploits sequences created in silico and then produces them chemically. In this, we can design plasmids, primers, recombinant DNA of our own choice, as per the needs of our experiments. To us it might seem insignificant today, but only when we understand the far reaching consequences of these tools, will we be able to truly appreciate it.
Basic Pipeline for Computational Approaches in Synbio experiments
Looking at software, many of them are available in which we can play with sequences. Some of them are SynBioSS, iBioSim, SnapGene, Escher (for biological networking). Also, SBML (Systems Biology Markup Laboratory) is a free and open standard software support for communicating and storing computational models of biological processes.
In a nutshell, computer aided design can help in designing the synthetic parts but it will be efficient only if it simplifies the design process. One of the main challenges involving in silico platforms is the isolation and standardization of the tools developed. Various repositories and registries around the globe are working collectively to make in silico platform of Synbio more integrated. Developments are continuing in this field, and with more such developments, the indispensability of such platforms for biologists are dawning clearer.