Applying Universality to Systems Biology

Over recent years, the field of “systems biology” has been emerging.  It is throwing light on areas that have long been a mystery.  There are also vast back catalogues of biological research that need to be reviewed from the perspective of systems biology.

Biology is often described as an empirical science with limitless detail, but every instantiation of experiment, observation, and classification is closer akin to an island embedded within an archipelago of unifying theory and commonalities. The most lasting innovations in biology are those that bridge the gap between (seemingly) disparate phenomena, crossing the threshold into new paradigms of insight and synthesis…. The present vista of possibilities for advances in mathematical biology extends outward e.g., protein structure to metabolic pathways to quorum sensing to population dynamics…The challenge that biology faces is to go beyond identifying life’s basic elements and to explain the emergence of biological organization at multiple scales…..mathematical themes (symmetry, duality, and stochasticity) could serve as means to unify problems and methods.  One of the fundamental challenges in biology is to explain the link between microscopic building blocks of individual organisms and macroscopic organismal/ecological phenomena within an evolutionary context . Moving from the micro- to the macro-scale requires a description of the non-equilibrium statistical mechanics of large assemblages of individual agents, in which the range of types is continuously evolving through the infusion of new diversity via mutation and other mechanisms. In a sense, stochasticity is embedded in the foundations of multiscale biology and may require concomitant work on novel formulations of appropriate mathematics…. Organisms do not require precisely tuned environmental conditions, they tolerate noisy inputs, sudden change, and competition robustness is a universal property of life. But, how different are the properties of systems in which robustness is selected for through natural selection from those where robustness is an emergent property…A major innovation in the mathematical foundations of the evolution of robustness would be a watershed moment for biology.  Princeton University. 

To truly push forward science, a universal approach must be taken that crosses all the sciences.  It is may not just be a question of physicists informing biology – biology may have something to tell physicists.  For biology allows us to observe what is taking place at our own scale – this provides an opportunity for direct observation that is not offer at other scales (i.e those scales most studied by physicists). It can be difficult for scientists who are used to operating on the basis of theory and laboratory based experiments to open their eyes and see.  And on a human level, it is difficult for us to move pass what we perceive as “reality” (and so societal and mental constructions).

Self organising criticality (SOC) and the renormalisation approach considers physics on all scales as equally important and strongly coupled … Central to the structure of such a model is self-similar scaling (the system looks the same on all scales subject to a rescaling), leading to power law distributions of (event) sizes and power law (long-range) correlations as the key observable. Importantly, a broad range of different detailed, microscopic interactions, on coarse-graining, lead to the same collective behavior, thus one expects the same essential phenomenology to be ubiquitous…Nicholas W. Watkins 2015.  

In this universe, what we call matter emerges as clusters created out of smaller clusters, and interact with clusters  at the scales above and below, and with clusters on the same scale.  Some clusters are loose, others are very tight, but they are all being subjected to the same forces. Nothing is allowed to remain the same for ever – the system is constantly introducing new elements to the clusters, breaking them apart, reforming them.   We see this happen directly to biological clusters at our own scaling, but the same thing is happening to clusters at other scaling.

New Challenges

Silo thinking had been encouraged in science for many decades for a number of reasons including: a mechanistic view of the universe, a focus on falsification, protected specialisms, laboratory based experimentation, and the sheer challenge of trying to read and understand diverse complex information.

More recently this has changed due to:

  • Commercial pressures, and the creation of cross cutting fields such as biotechnology and computing.  Here there is an awareness of highly complex adaptive systems, and the need to focus on “making it work”- rather than falsification.
  • The increasing availability of scientific research i.e on the internet and globally available.
  • The increasing questioning of some scientific models, which no longer stand up to close scrutiny – as research reveals new challenges to those models.  These challenges are not necessarily simple falsification, rather they can suggest that models may need to be extended.
  • Growing awareness of the validity of “self organisation”.
  • The emergence of cross disciplinary teams.

Seeking Universality 

For the past few decades there have been movements within science towards the study of open and complex adaptive systems.  These potentially span areas and fields of science that were previously separated.

Now we have to move beyond all the labels we have given to things in order to distinguish them from one another and make them “special” (specialisms) and start looking for the similarities (the universal) and correspondences.

This includes cutting edge fields such as quantum biology, but also movements within physics to bring together fields e.g high energy physics, string theory, condensed matter physics and holography brought together through AdS/CMT.   Recently AdS/CFT has been used to provide insight into the evolution of far from equilibrium systems to equilibrium.

Biology and Chemistry can Inform Physics

Indeed you will find words like swarming within some fields of physics e.g to describe collections of particles such as gluons.  And there is the potential for biology’s understanding of the world to further inform understanding of physical collectives at all scales.

Models of collective oscillations in organisms (from bacteria to humans) also offer important insight for understanding far for equilibrium dynamics.

Stochastic reaction-diffusion simulations have been successfully used in a number of biological applications.   Formation of skin patterns and the biochemical processes in living cells (like gene regulatory networks), the cell cycle, and circadian rhythms, signal transduction in E Coli chemotaxis, MAPK pathway, oscillations of Min proteins in cell division, and intracellular calcium dynamics are examples of processes mathematically modelled by reaction and reaction-diffusion systems.

Cell Cycles are interacting with circadian rhythms and intercellular calcium dynamics, – and perturbation of the transcription–translation feedback loop clockwork or the redox system results in a perturbation of the other, indicating that they have a reciprocal relationship.  It is a system of self organisation.

P Mehta 2010 provides a table of synchronised oscillations models in biology:

coupling

Physics can inform biology

A long-lived electronic quantum coherence has been observed in a light harvesting protein (the Fenna-Matthews-Olson (FMO) complex)  (Brixner 2005 Nature, Engel 2007 Nature). The initial experiments were carried out at 77 K, but more recent studies by two groups have detected coherence lasting at least 300 fs at physiological temperatures (Engel 2010 PNAS, Scholes 2010 Nature).

In the Fenna-In Matthew-Olson (FMO) pigment-protein complex  microsecond triplet excited-state energy transfer between the bacteriochlorophyll (BChl) pigments, but show no evidence of triplet energy transfer to molecular oxygen, which is known to produce highly reactive singlet oxygen and is the leading cause of photo damage in photosynthetic proteins. S Kihara – ‎2015.  A similar effect is found in Rhodobacter sphaeroides. P Rebentrost. 2009.Xian-Ting Liang 2010, and some plants.

A radical pairs mechanism has also been found to operate in photosynthetic reaction centres (where evidence has also been found of quantum mechanics potentially assisting the process of electron transfer).  

This has been referred as the photo-CIDNP effect.  During charge separation in photosynthetic reaction centres, triplet states can react with molecular oxygen generating destructive singlet oxygen. The triplet product yield in bacteria and plants is observed to be reduced by weak magnetic fields.  It has been suggested that this effect is due to ‘solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP ), which is an efficient method of creating non-equilibrium polarization of nuclear spins by using chemical reactions, which have radical pairs as intermediates e.g see   I K. Kominis 2015.

A ‘solid-state photo-CIDNP effect’ has been observed in:

Previously it had been proposed that such effects were a quantum zeno effect. E Daviso 2009A T Dellis and I K Kominis, 2009 A.T. Dellis, I.K. Kominis 2011,I K Kominis 2013, And perhaps this effect can be seen as analogous to the quantum zeno effect. When the quantum zeno effect is manifested (i.e. when the recombination rates are asymmetric), the reaction’s magnetic and angular sensitivity is practically independent of the presence or not of exchange and/or dipolar interactions A.T. Dellis, I.K. Kominis 2011.   

The effect also reduces oxidative stress in bacteria and plants and so offers an important anti-oxidant effect. Marais et al 2015),

It has been noted there seems to be a link between the conditions of occurrence of photo-CIDNP in Reaction centres and the conditions of the unsurpassed efficient light-induced electron transfer in Reaction Centres. J Matysik 2009,   I F Cespedes-Camacho and J Matysik 2014.  This may be because a electron transfer protein (e.g consisting of both a flavin and iron sulphur cluster) may be leading to ultra fast electron transfers.

A solid state Photo-CIDNP effect has also been demonstrated on the photochemical yield of a flavin-tryptophan radical pair in Escherichia coli photolyase. K B Henbest 2008, and a solid state photo CIPNP effect has been observed a mutant of the bluelight photoreceptor phototropin (LOV1-C57S from Chlamydomonas reinhardtii). S S Thamarath 2010.

In the same way that photo-CIDNP MAS NMR has provided detailed insights into photosynthetic electron transport in reaction centres, it is anticipated in a variety of applications in mechanistic studies of other photoactive proteins. It may be possible to characterize the photoinduced electron transfer process in cryptochrome in detail. W Xiao-Jie12016.

Until recently solid-state photo-CIDNP effect has required high magnetic fields and cyclic electron transfer, which is reached, for example in RCs of Rb. sphaeroides by reduction or removal of the quinones.  But it has also been speculated that solid-state photo CIDNP effect at earth field plays a role in the magnetoreception of biological systems….Studies have found that the ‘solid-state photo-CIDNP’ effect allows for signal enhancement of factors of several 10000 s. Such strong signal enhancement allows for example selectively observing photosynthetic cofactors forming radical-pairs at nanomolar concentrations in membranes, cells, and even in entire plants. W Xiao-Jie12016.  Also see G Jeskchke 2011.  

And beyond ultrafast charge separation in photosynthesis, there are similar dynamics in bond isomerization in sensory photoreceptors and repairing DNA damage.  It should be noted that in the DNA repair enzyme photolyase, it has been found that maximum efficiency was not enhanced by the ultrafast photoinduced process but by the synergistic optimisation of all steps in the complex repair reaction. C Tan 2015.   

In addition iit has been discovered that putting certain types of bacteria into an ordinary fluid can cause it to become a superfluid.  Héctor Matías López 2015.   Superfluidity is found in astrophysics, high-energy physics, and theories of quantum gravity.

 

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Rhythms as Universality

“The periodic physiological phenomena that exist in nature have been quantified, and there is a developing consensus that these rhythms are synchronised from the level of the cell to that of swarms, from periods of millisecond duration to rhythms spanning millennia..it is logically consistent with the evolution of the genome from its seminal progenitor (LUCA) and its requirements, like all machines, for a master time setter.  Moreover an evolutionary advantage will be imparted to those chromosomes that can time their activities of their organism to exploit the earths periods…just as we gaze at a star and from its wiggles deduce the structure of a distant solar system, so in an anologous fashion we can discern precisely how biological rhythms influence each other and how these rhythms synchronise biological systems”.  T Glonek et al edited by A G Chila 2010.

But at biological and universe scale, there must be an integration of space-time, magnetism, gravity, etc.  Phase transition may be at the heart of this.

Circadian rhythms have been modelled in several ways.  This has included as:

When time and space are heated, an expanding universe can emerge without a ‘big bang’.  This involves a phase transition in empty space and an expanding universe containing mass.  Phase transition in quantum field theory is well known, but for symmetry reasons this would mean that gravitational theories should also exhibit phase transitions.   This work has been developed by Daniel Grumiller (TU Wien).

Universality and Specialism 

We reached an extreme in “specialist” thinking and are now being drawn back towards universal approaches.  This will not be an end to it.  Once an extreme is reached in “universality”, it will be time to start focusing on the differences again.  All human philosophies are subject to ebbs and flows: political systems, economies, etc – scientific thinking is part of this system.

2016.  This article merely joins up other peoples work into an overall system.  These works have been referenced so it is clear that others have provided the individual pieces of evidence that have been used to shape a specific systems approach.    

 

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