Funded research

The Guy Foundation played a key role in thinking up the notion behind this project, through convening and contributing to the interaction and cross-talk between cutting-edge scientists in the Foundation’s online lectures. The lectures advance beyond the confines of engrained thinking and consider profound questions at the nexus of physics and biology. Fascinated by the question of bioelectricity and ATPase function in one such lecture session, the Foundation instigated discussions with Professor Michael Levin and Professor Wayne Frasch and was instrumental in shaping this collaborative research project. The Foundation has a longstanding interest in mitochondrial function including the role of ATPase and is also already funding research into bioelectricity and its role in host reprogramming.

Birth defects, traumatic injury, and other dysregulations of body anatomy such as aging and cancer could all be addressed if we solved one major open problem: how to control which complex structures cells will build. Despite the advances in stem cell biology and genetics, many important knowledge gaps still exist about the origin of body form.

Recent advances suggest that part of the answer lies within the bioelectrical communication among cells. All cells, not just neurons, establish networks that generate specific patterns of standing resting potentials in tissue. These are present from the earliest (1-cell) stage of embryogenesis and the earliest steps of regeneration after injury (in regenerative species).

The Levin lab, at Tufts University, developed the first molecular tools to listen in and modify the electrical conversations that cells carry out in vivo. They (and others) showed that these bioelectric patterns are instructive for growth and form: when disrupted or modified, predictable changes to gene expression and anatomy are induced. What is the origin of these patterns?

Several papers from the Levin lab indicate that the presence of the V-ATPase proton pump on the plasma membrane participates in several aspects of large-scale anatomical control, including regeneration of appendages (and spinal cord), left-right asymmetry, etc. Indeed, the one gene that regenerating systems across Kingdoms of Life turn on after amputation is a V-ATPase component. V- ATPase has also been implicated in the morphogenetic defection known as cancer. Isoforms of V- ATPase carry out several functions in organelles and the plasma membrane that are species-specific.

The Frasch lab, at Arizona State University, has studied how modulation of assembly factors vary the density of V-ATPases in the plasma membrane. The V-ATPase proton pumping activity that generates cell membrane potential is strongly regulated by cellular energy level including glycolysis and oxidative phosphorylation. This ancient electrogenic protein is an ideal candidate for tracking the origin of the physiological dynamics that set morphology.

However, in embryos, these dynamics are obscured by the complexity of the body plan and the biomechanics that fold tissue in ways that make tracking bioelectrics very difficult. It is essential to establish a model that is simultaneously complex enough to exhibit bioelectrically-driven development but simple enough to facilitate imaging and computational modelling of the multiscale dynamics leading from V-ATPase function to whole body form. The Levin lab has established a simplified developmental model: the Xenobot. This synthetic proto-organism self-assembles from piles of loose skin cells, and becomes a motile creature with both unitary and group behaviours, as well as a specific developmental sequence over its several-week lifespan.

The team will study the expression and function of the V-ATPase during the self-assembly and developmental stages of the Xenobots, correlating it to bioelectric and metabolic patterns. They will also incorporate transformed (cancer) cells, which do not obey the morphogenetic plan. In this highly tractable new context, they hope to understand how the energetics of the V-ATPase proton pump dictate the structure and function of new tissue, and establish an important foundation for exploiting this knowledge in biomedicine relevant to developmental disorders, regenerative repair, and cancer.

About the Allen Discovery Center at Tufts University:

The Allen Discovery Center at Tufts University focuses on reading and writing the Morphogenetic Code, which orchestrates how cells communicate to create and repair complex anatomical shapes. For more information, visit https://allencenter.tufts.edu/

About the Frasch lab at Arizona State University:

The Frasch lab investigates the rotation of molecular motor proteins, with a focus on the Fo and F1- ATPase rotary motors that comprise the FoF1 ATP synthase. This protein complex is responsible for producing the majority of adenosine triphosphate (ATP), whose energy rich bonds provide most of the energy for cellular processes.

For more information, visit https://www.thefraschlab.org/

It is now generally accepted that all life, whether it is a bacterium, a plant, or a human, produces very low levels of light during both normal metabolism and especially when under metabolic stress. As the number of these photons is very low, and thus not visible to the naked eye, they are known as “ultraweak photons” or “biophotons”.

A key focus for the Centre for Optimal Health at the University of Westminster is to study the role of mitochondrial health and how hormesis controls health span, which suggests that investigating the relationship between biophotons, oxidative stress and mitochondrial function could be a valuable path to pursue. At a deeper level it has been suggested that photons, fundamental quantum entities, could be pivotal in understanding the extent that life is using quantum mechanics. Thus, the proposed research project will investigate the potential role of biophotons in senescence, a fundamental cellular event associated with health and disease.

Photonic and electromagnetic manipulation of living systems is a rapidly developing field of medicine, one in which The Guy Foundation is playing a key role in developing, both from the basic scientific point of view, but also in the future development of modern therapeutics based on a deeper understanding of quantum thermodynamic principles in biology. The proposed project builds and expand of current research under the auspice of the Foundation.

Some animals regenerate complex organs after injuries (for example, salamander limbs and eyes, human livers, and deer antlers). The remarkable part of this process is not simply that cells can rebuild appendages that are functional and perfect copies of the original. It is that cells can start at different configurations (e.g, limbs amputated at different levels), arrive at the same final anatomical configuration, and stop the growth and remodeling process when they are done. This process of anatomical homeostasis requires the cellular collective to be able to detect when the correct large-scale target morphology has been restored. While the genome specifies the protein hardware that every cell can deploy, there is a critical open question: what biophysical mechanism encodes the stop condition, and can it be altered? How much plasticity exists in the shape toward which cells build, and could this pattern be altered without genomic editing? The question of anatomical plasticity and robustness is important for: 1) fundamental knowledge of evolution of bodyplans, and 2) regenerative medicine approaches to induce morphogenesis of needed structures (in vitro or in the patient) for applications in birth defects, traumatic injury repair, aging, and tumor reprograming. It is essential to understand how tissues store and process information about what morphology they should construct.

Recently, our group made a surprising discovery. In planarian flatworms – an important model for regeneration – the number of heads that each fragment creates after injury is determined by the state of an endogenous bioelectric circuit. Using ion channels and gap junctional synapses, tissues store a physiological pattern that dictates the number of heads. We showed that transient alteration of this bioelectric state (by targeting native ion channels and gap junctions) induces a 2-headed planarian that continues to regenerate as 2-headed, without further intervention and without any genomic editing. This revealed remarkable plasticity of wild-type cells and a new path to understanding the encoding of target morphologies for regenerative processes.

In recent months, we have discovered new ways to change the pattern toward which planarian cells build. This gives us the unique opportunity to understand how regenerative target information can be permanently altered in vivo and how this information spreads through the host body to dominate the prior state. We will undertake a 2-year project (a mix of regenerative biophysical benchwork and computational modelling, targeting molecular mechanisms of physiological software) to: understand the mechanisms by which cells coordinate target information body-wide, and develop quantitative models to understand the logic by which bioenergetic processes enable a cellular collective to make large-scale morphogenetic decisions. In our lab, such information can be (and is being) translated into new approaches for regenerative therapies targeting injuries too complex to be micromanaged directly with stem cells or gene therapy.

About the Allen Discovery Center at Tufts University:
The Allen Discovery Center at Tufts University focuses on reading and writing the Morphogenetic Code, which orchestrates how cells communicate to create and repair complex anatomical shapes.
For more information, visit https://allencenter.tufts.edu/

Light is fundamental to the origins and development of life. Out of need for protection from solar ultraviolet (UV) rays, organisms have employed a variety of mechanisms to absorb and transfer UV radiation, including with small plant compounds. A hallmark of these compounds—shared by several basic constituents of proteins and nucleic acids—is their “aromatic” structure due to delocalized π electrons. Highly ordered networks of aromatic amino acids and nucleobases are integral to the formation of important cellular structures in mitosis and other biomolecular processes. We have predicted from quantum mechanical calculations that the native symmetries of such aromatic mega-arrays conspire to produce a superradiant effect, whereby a group of N quantum two-level systems interacts collectively with a common light field to emit high-intensity pulses with rate proportional to N². Using ultrafast UV fluorescence up-conversion and two-dimensional transient absorption spectroscopy, we intend to experimentally validate this prediction in the model playground of tubulin architectures, from the protein heterodimer to polymerized microtubules to microtubule bundles and the centriole. Using non-Hermitian quantum mechanics, density functional theory, and high-performance computing techniques, we will also develop novel theory and models for treating mega-arrays with distinct types of chromophores and for closely spaced geometries. Our results have serious implications for mitochondrial function, as reactive oxygen species produced during aerobic respiration can emit ultraweak UV light. These UV photons would be transmitted coherently by these aromatic lattices, thus potentially forming quantum optical signalling pathways in the cell.

About the Quantum Biology Laboratory (QBL) at Howard University:
With a transformative vision that extends from the subatomic to the clinical scale, the QBL studies how collective behaviours in living matter can be manifested, controlled, and exploited for the development of advanced tools, diagnostics, and therapies to address neurodegenerative, oncological, immunological, and oxidative metabolic disorders.
Investigators in the QBL use tools from theoretical physics, condensed matter, quantum optics, molecular biology, biochemistry, genomics, spectroscopy, and high-performance computing to solve an array of problems relevant to human disease processes and clinical medicine.
The research team includes: Philip Kurian, Ph.D., Principal Investigator and Founding Director; Muneer Abbas, Ph.D., Associate Professor of Microbiology; Georgia Dunston, Ph.D., Senior Advisor and Professor Emerita; Matteo Gori, Ph.D., Postdoctoral Scholar; and Dana Plair, MBA, Executive Assistant. For more information, visit www.quantumbiolab.org

The Health Care Worker Covid-19 study is being led by Barts Health NHS Trust in collaboration with the London Nightingale Hospitals, UCLH, the Royal Free and Queen Mary University of London.

This important and urgent study will generate a national bioresource with over 200,000 blood and swab samples that will be shared with the UK's leading research groups as they try to deliver answers to some of the most pressing questions for tackling COVID-19 infection. Led by Professor James Moon and, the study will track 1,000 frontline healthcare workers to examine baseline immune function, earliest immune responses to infection, and the biology of those who get non-hospitalised disease to help researchers find new ways of identifying, safeguarding, treating and preventing infection.  This is vitally important since the modelling currently informing all strategies is based on pandemic influenza, not COVID-19.

At Harwell, the primary aim is to directly image cells, and potentially mitochondria, using their own nascently produced biophotons and to investigate the processes that generates them, and how this interacts with electromagnetic (EM) fields – and potentially, whether or not this is a quantum mechanical process.

Although biophotons have long been observed using sensitive cameras, and their existence demonstrated by the ability of one group of cells to communicate with another using biophotons, their direct observation has only been at the level of the organism/tissue on a macroscopic scale. This is because the numbers of biophotons produced per cell, detectable by the technology in the last 50 years, was thought to be only around 1-10 photons per second. However, more recent estimates derived from how they might be generated in relation to oxidative stress does indicate it could be a lot higher than this – especially inside the cell. For instance, it could be well over a million per second in retinotropic visual neurons. It is thought that they are being produced via mitochondrial redox/free radical processes, which suggests that redox signals can be converted into biophotonic signalling. Hence, it is possible that the amount of biophotons produced within the cell is much higher than detected outside, and that the mitochondrial network could play a key role in biphotonic communication – but imaging these is a serious technological challenge (Bokkon et al., 2010). That enough biophotons are emitted to affect other cells does suggest it could be a viable biological communication process (Mayburov 2012).

However, with advances in technology, it may now be possible to image individual cells, and even mitochondria, using their own biophotons. The laboratory at Harwell specialises in advanced microscopy and has already demonstrated the ability to study mitochondria using a laser-based technique called fluorescence lifetime imaging (FLIM). This technique provides both good images of mitochondrial structures, but also their metabolic state, and has already shown that compounds like cannabidiol can alter these parameters (Mould et al., paper in preparation). By combining the latest microscopy techniques with the latest high sensitivity detectors, spectral analysers, data analysis and FLIM techniques, and dyes sensitive to EM fields, it may be possible to start confirming theories involving the relationship between biophotons and their wavelength, mitochondria, EM fields and free radicals in live cells. Furthermore, preliminary experiments suggest it may also be possible to detect solvated electrons produced during oxidative stress. Finally, using a new process called “ghost imaging” (Erkmen and Shapiro, 2010), which relies on entangled photon pairs, as well as a technique to study entangled photon-electron pairs, it may become possible to answer whether or not the above processes are quantum mechanical in nature, and in particular, whether compounds like cannabidiol alter them. In short, it may be possible to not only image cells using biophotons, and confirm that biophotonic communication may well be a normal part of cellular functioning, but whether or not it could be quantum in nature, and potentially, whether or not the mode of action of some compounds might encompass modulation of quantum effects.

At Westminster, the primary goal is to confirm that biophoton production in individual cells and mitochondria can be used as a means of communication between them, and therefore confirm the observations of other researchers – and then study how well known medicines, in particular, natural products, modulate this process.

This will be initially achieved by studying whether or not cells, or isolated mitochondria, placed in separate cuvettes, can influence each other using light when the cells in one cuvette are challenged in a way that alters their metabolism – in particular, under stress, and then see if the cells in the other cuvette respond. The cell’s metabolic status will be followed by measuring their respiration (their oxygen consumption). Once this method is established, variables, such as distance and light frequency (by putting different light filters between the cuvettes), fuel types (for instance, fats versus glucose), and the effects of electromagnetic fields, will be investigated. The next step will then be to study cell to cell light communication under a new high resolution microscope that enables imaging of multiple dishes, so further parameters can be followed, such as mitochondrial shape, calcium flux, hypoxia, and how healthy and diseased cells compare and potentially communicate, and then see how this communication is effected by medicinal compounds and metabolic inhibitors that can induce oxidative stress.

Overall, the goal is to confirm, at the macroscopic scale, that cells not only produce biophotons, but that they can influence other cells, indicating that a form of biophotonic communication is active in live cells. A key part of the experiments will be to study how this relates to bioenergetics, and potentially, how compounds that may absorb light, exogenous light of particular wavelengths, and electromagnetic fields, modulate mitochondrial function and inter-cellular communication.