Universality in Biology

Biology: Amyloid fibrilisation | Physics: Living polymeric systems
Amyloid fibrils are fibrous aggregates of proteins (Fig. 2A). Amyloids are intimately related to numerous human diseases including Alzheimer’s, Parkinson’s and type II diabetes. In the past decade, I have investigated theoretically the phase behaviour of amyloid-forming proteins [1], the universal kinetics of fibrilisation at the high bonding energy limit [2], the critical importance of interfacial effects on amyloid formation in-vitro [3–6], and the phenomena of gelation and phase separation in amyloidogenesis in vitro [7,8]. Many of these works were carried out in close collaboration with the Vaux group in the Dunn School of Pathology at Oxford. We are now in the position to build on our findings to understand amyloid pathogenesis in vivo, which to date remains a mystery to scientists. To make the in-vitro to in-vivo leap, we will need to consider fibrilisation in the far-from-equilibrium regime, in which proteins are continuously produced, degraded, and transformed through post-translational modifications. Studying the physics of these ‘living’ polymeric systems will hold the key to understanding how amyloid fibrilisation occurs in vivo and hence how amyloid diseases arise.

Biology: Intracellular organisation via phase separation | Physics: Non-equilibrium phase separation
The survival of a biological cell relies on the proper functioning of its interior subunits called organelles. Since 2009 [9], there has been an explosion of studies on non-membrane bound organelles that form via phase separation (Fig. 2B). Indeed, the realisation of phase separation as a major mechanism in cytoplasmic and nucleoplasmic organisation has revolutionised cell biology and promises to rewrite textbooks in biology. The theory of phase separation in equilibrium is well established, but the highly non-equilibrium nature of the cellular environment (e.g. the presence of many ATP-hydrolysis-driven processes) renders the standard equilibrium theory obsolete. However, there is a near void of knowledge on phase separation in the non-equilibrium regimes. For example, one recent surprise is that in a driven phase separating system, the well-known universal Liftshitz-Slyozov scaling law [10] that governs the coarsening behaviour in equilibrium systems can be violated [11,12]. I have been at the forefront of the study of non-equilibrium phase separation in the context of cell biology [12–15], and have co-authored two recent reviews on this topic [16,17]. However, a comprehensive theory of cellular phase separation is still missing and formulating such a theory is a research focus of my group.

Biology: Active cell, tissue, and organism dynamics | Physics: Active matter
Motility is a fundamental hallmark of living organisms (Fig. 2C). Understanding such active matter is essential to our understanding of organismal morphogenesis, wound healing, animal dynamics, and bacterial colonies. Besides its omnipotent importance to life sciences, the study of active matter has turned out to be a gold mine of novel transitions and phases. In the past five years alone, I have co-discovered, using analytical renormalisation group methods, two new universality classes: one describes a novel critical phenomenon in incompressible active fluids [18], and a second defines a new non-equilibrium state of matter [19]. Classifying many-body dynamical systems by the universality classes they belong to is akin to classifying elements by their atomic numbers in the periodic table. I will strive to continue to map out the distinct universality classes associated to active matter.

Besides discovering new physics in active matter, to complete the circle in Fig. 1, I am also applying the theory of active matter to understand diverse biological systems. These include the elucidation of the relationship between the active dynamics of the cell cortex and intracellular pore formation in the context of glaucoma pathogenesis with bioengineer Prof Darryl Overby (Imperial College), and the study of stem cell regeneration and localisation in the bone marrow with Prof Cristina Lo Celso (Imperial College) from the perspective of motility-induced or motility-enhanced phase separation.

Figure 2: (A) Biopolymer self-assembly. Amyloid fibrils self-assembled from the Abeta proteins, which are implicated in the pathogenesis of Alzheimer's disease (Figure taken from [5]). (B) Non-equilibrium phase separation in the cell cytoplasm. The organelle P granules (green) localise to the posterior of a C. elegans embryo at the one-cell stage (Figure taken from [9]). The formation and localisation of P granules result from non-equilibrium phase separation [13]. (C) Viewing wound healing assay as an active matter system. A monolayer of cells will fill a gap through active motility and proliferation. At the coarse-grained level, the dynamics of the system may be described by the Toner-Tu equations that describes universally active fluids in the same way that the Navier-Stokes equations govern universally the dynamics of passive fluids.

Vision
I have outlined above my broad research programme for the next five years in the context of three specific biological problems. The keywords common to all these examples are universal, non-equilibrium, and phase transition. This is why I named my research group Universality in Biology, with the goal to elucidate universal behaviour in biological processes that are naturally and intrinsically in the non-equilibrium regimes. Our endeavour is not only of fundamental interest to physicists and of crucial importance to biologists, but is also of significant value to the design of functional active materials. Indeed, the advent of bioengineering has enabled researchers to better design, manipulate and control living matter, with examples ranging from microbial cell factories to tissue engineering. This newfound capability mirrors the arrival of semiconductor materials by design several decades ago that propelled condensed matter physics to become the ‘king’ of physics since the 60s [20]. I strongly believe that biological physics will become the next ‘condensed matter physics’.

One the biology side, the study of universality will enable us to link seemingly unrelated biological systems, produce quantitative predictions that do not depend strongly on the microscopic details, and explain the emergence of system-level dynamics and properties. I expect that in the near future every biologist will be aware of the concept of universality and may even know which universality class the biological system they are studying belongs to.