Our understanding of the physical world is impressive. It includes, for instance, both detailed knowledge about the history of the universe and a comprehensive understanding of the building blocks of matter. But despite these advances, we don't yet have a comparably deep understanding of how those building blocks lead to life and organisms.
How can life emerge from an information-processing matter system? Do the principles that guide order-generating processes in nature also underly the development of functional structures in organisms? What key functions distinguish living from nonliving systems and how might these functions be realized using a range of matter platforms? Answering these and related questions that probe the distinctiveness of life constitutes a grand challenge where breakthroughs can have outsized impacts for both science and society.
Today we recognize that the distinctiveness of life is not to be found in some unique type of matter comprising organisms, but rather in the novel ways in which matter is organized within living systems, the most complex arrangements of matter known. Understanding these distinctive modes of organization means identifying the novel functional capabilities exhibited by organisms and understanding how those functions are realized. Achieving this understanding will shed light on the matter-life nexus. While the matter-life boundary is not sharp, well-chosen scientific explorations can play an important role in helping to identify significant milestones along the transition from nonliving to living matter.
Sloan's Matter-to-Life program aims to sharpen our scientific understanding of life by supporting curiosity-driven research falling within three focus areas: Building Life, Principles of Life, and Signs of Life. These areas define a broad scientific scope for understanding the physical principles and mechanisms governing living systems, while also highlighting an openness to exploring life broadly conceived by instantiating the distinctive functions of living systems in entities built using various matter platforms. The program will also support scientific meetings that promote information exchange, the development of collaborations, and self-organizing efforts aimed at making a case to other funders for supporting matter-to-life research.
We're hopeful the long-term impact of the program will be that we've rallied a community to start new lines of research that ultimately lead to a deep scientific understanding of life that explains both its physical distinctiveness and any processes that guide the complexification of matter towards life.
Research grants in Sloan's Matter-to-Life program seek to advance theoretical and experimental efforts aimed at unraveling the physical principles and mechanisms that distinguish living systems from inanimate matter, and that explore whether and how physical principles guide the complexification of matter towards life. The program will prioritize those projects making the most compelling case for how the proposed research will advance our scientific understanding of life's distinctiveness, and that pursue research directions not already well supported by federal funders. The program will not support biomedical or disease-related research. We seek to support well-conceived biology/physics/chemistry/engineering projects that explore the matter-life boundary in comparatively simple systems, rather than animal-based or social-science experiments that study complex higher-level organism behaviors. We recognize that both multi-disciplinary and exploratory work is needed to advance matter-to-life science, and the program is open to projects with these features when they are important to advancing the proposed science.
Grantmaking proceeds along three interrelated focus areas. Supported projects may involve any or all of the following:
Projects in this focus area attempt to learn about life by trying to construct it. Supported projects seek to advance our understanding of the matter-life boundary by constructing artificial (synthetic biological or abiotic) microscale systems that either teach us about important life-sustaining processes or lead to entities that mimic key life-like behaviors.
Grants could, for instance, support efforts to build protocells or other entities suitable for studying far-from-equilibrium processes or other processes important to life but which are too complex to study within natural cells. For grants that seek to build entities that demonstrate life-like behaviors, investigators will propose a set of life-like behaviors whose implementation in a given platform is both achievable and provides significant insight into living systems. Example behaviors include replication, metabolism, evolution, environmental sensing and information-processing that leads to adaptive behavior or cooperative community behavior. Achievable life-like behaviors will be platform-dependent, and grants will seek to stimulate the development of platforms that eventually produce bio-inspired entities leveraging hierarchical design and self-assembly principles to achieve structure and function.
Sample research questions in Building Life include:
- Can abiotic matter systems be developed that leverage information stored in submicron building blocks to self-assemble, replicate, metabolize, heal, or adapt?
- Can we build nanoscale molecular machines capable of complex motions and functions that compare to those exhibited by the molecular machines of life?
- How does one build a macroscopic structure using hierarchical design principles and submicron building blocks?
- Can synthetic cell communities achieve complex functions cooperatively through local cell-cell interactions?
- Can we build a live synthetic cell?
Projects in this focus area attempt to identify the key physical principles that govern living systems broadly conceived by identifying the principles governing biological organisms. The program is open to supporting both reductionistic and top-down efforts. Reductionistic approaches seek to determine the detailed, often nanoscale, mechanisms by which organisms realize their essential functions. Here the program will favor supporting underappreciated approaches for unraveling the mechanisms of biology such as biomechanics, fluid dynamics, and thermodynamics. The program will also support top-down efforts to identify the emergent phenomena exhibited by living systems. Here the goal is to develop comparatively simple models that provide explanatory and predictive power at the level of the emergent phenomena, without resort to more fine-grained processes or mechanisms.
For both approaches, the ultimate goal is to uncover the key organizing principles and mechanisms that must be implemented in any platform to achieve a living system. We expect that working towards this goal will lead to the discovery of new physics, particularly new emergent physics exhibited by the class of complex systems within which organisms reside as distinctive, far-from-equilibrium physical systems.
Sample research questions in Principles of Life include:
- Does nonequilibrium physics contribute to the development of structure across scales in biology?
- Can we understand and control how simple molecules evolve under environmental pressure to more complex functional molecules?
- Can scale-invariant physics be identified in living systems?
- Can we gain a comprehensive, quantitative understanding of how cells use entropy to maintain themselves as stable entities far from equilibrium?
- Are state-dependent laws needed to describe life?
Projects in this focus area attempt to sharpen our understanding of the distinctive signatures associated with living systems by identifying such signatures, quantifying these signatures, and exploring the physical principles and mechanisms underlying these signatures.
Projects that propose to identify signatures will develop platforms or methods aimed at reliably detecting the presence of life. Relevant efforts could, for instance, include research to determine signatures of life on other planets. Projects that propose to quantify signatures will work to develop quantitative metrics that could be used to distinguish living from nonliving systems, or to develop predictive models that quantitatively describe signatures of life. Projects that propose to examine the principles and mechanisms underlying signatures will explore models to describe these signatures with an eye towards making connections between order-generating processes in inanimate matter and the ordered structures and processes found in organisms.
Sample research questions in Signs of Life include:
- Can evolutionary adaptation be understood as a special case of a more general principle describing how complex systems evolve in response to environmental change?
- Are there quantitative metrics that can be used to distinguish living from nonliving systems?
- Are there atmospheric signatures of life?
- What are the physical principles underlying various life-like behaviors of organisms?