Postdoctoral Fellows

Adam, Zachary

Zachary Adam, Ph.D.
Education: Montana State University, Ph.D., Geology
Institution: President & Fellows of Harvard College (laboratory of Andrew Knoll)

Project: Geologic production of polymer-forming solvents on the prebiotic Earth

All living organisms require water to survive, but water also gradually degrades nearly all of the molecules that make us alive. As a result, all organisms spend a substantial amount of energy repairing and re-forming molecules like DNA, RNA and proteins, so they can remain alive. In light of the damaging effects of water, and the special steps life has to take to fight against them, it is difficult to imagine how life emerged on the prebiotic Earth. To get around this difficulty, some scientists have proposed that instead of exploring unlikely ways that prebiotic chemistry can be carried out in water, we should look for alternative liquids that follow different chemical rules than water. Specifically, it has been proposed that water-based life derives from even older chemical reactions that took place in a liquid called formamide. Formamide physically behaves like water in many ways, but chemically, it allows reactions to take place that lead to the production of molecules like RNA and proteins that are very unlikely to occur in water. However, it is not clear how formamide could have been formed in abundance on the early Earth.

I recently formed a team that found a way to produce abundant formamide and a sugar molecule called glycolaldehyde in a setting called a placer deposit, which is a location where dense minerals are concentrated due to waves or water currents. The dense minerals in placer deposits also include phosphate minerals. These are particularly promising discoveries because the three kinds of molecules that are found in RNA (nucleobases, sugars and phosphates) can theoretically all be produced in this one kind of geological setting. However, it is unknown if each of these three kinds of molecules can be produced at the same time and under realistic, naturally occurring conditions. If we can make all of the RNA compounds in a single setting from abundant starting materials, then we can create testable hypotheses to explore whether RNA can be formed from geochemically driven reactions and whether these reactions can lead to life forming on our planet. For these reasons, I propose to investigate placer deposits as one possible example of a setting that could have produced RNA on the early Earth by using experiments that mimic the physical and chemical conditions inside these sediments.

 

Blättler, Clara

Clara Blättler, Phil
Education: University of Oxford, DPhil., Earth Sciences
Institution: Princeton University (laboratory of John Higgins)

Project: Ca and Mg Isotopic Indicators in Ancient Carbonates

This proposal introduces two new geochemical tools to the search for evidence of the earliest life on Earth and the environments it may have inhabited. The tools for this research will be the stable isotope ratios of calcium and magnesium, which are major components of limestone and dolomite rocks and hold promise as proxies for recording early microbial activity and marine conditions. Substantial work on both modern analogue environments and theoretical considerations suggests that this approach can introduce valuable new dimensions to long-debated problems on the chemical composition of seawater during the early evolution of life and the biogenicity of minerals in the ancient (> 2.5 billion year old) rock record. This work is directed at answering two major questions: 1) did the earliest oceans resemble modern soda lakes, rather than the sodium-chloride-rich oceans of today, and 2) can the presence of microbial activity be identified through a characteristic isotope signal in ancient sedimentary deposits.

 

Paul Carroll

Paul Carroll, Ph.D.
Education: California Institute of Technology, Ph.D., Chemistry
Institution: Smithsonian Astrophysical Observatory (laboratory of Michael McCarthy)

Project: Exploring the Cosmic Origins of Chiral Molecules

One of the most fundamental and fascinating questions of modern science is: How did life begin on Earth? In the course of studying the fundamental workings of biological systems, scientists noted an asymmetry in the way life employs handed molecules; that is, molecules whose mirror image is not the same as the original. These molecules, referred to as chiral, are integral to biology. This asymmetry, termed homochirality, is the biological use of only one of the possible mirror images, or enantiomers. Employing only one enantiomer affords numerous evolutionary advantages, and is found in every living thing. This asymmetry is the same across the biosphere, that is, all living things not only employ only one enantiomer of many molecules, they employ the same enantiomer. One of the great mysteries of homochirality is that enantiomers are virtually identical, having the same physical properties. This raises the question: How did life choose the handedness it did when faced with seemingly identical choices? Many processes have been proposed that could generate a small asymmetry, or excess, in enantiomers on the early Earth that drove homochirality. The possibility that interests me, and that is the central topic of my proposal, is that the primordial material from which Earth was assembled contained chiral molecules with this small enantiomeric excess.

It has been shown that meteorites contain amino acids, the building blocks of proteins, which contain a small enantiomeric excess and are therefore a plausible origin for homochirality. As an astrochemist, I am interested in how this enantiomeric excess came to be. Using radio astronomy, I study the molecular content of star-forming regions, the nurseries from which solar systems are born. The goal of my research is to characterize where and how the organic material in these regions comes to be, and how it becomes part of the solar systems that form from it.

Recently, I detected the first chiral molecule outside our solar system, propylene oxide. This molecule at last provides a target we can study to learn how chiral molecules may form and what astrophysical processes may create enantiomeric excess. My research as a SCOL postdoctoral fellow will build the foundation necessary to carry out these studies through two projects. First, studying enantiomeric excess requires a type of observation never before conducted. A first step in planning such observations is demonstrating they are feasible in the lab. Accomplishing this will be a major goal of my work. Second, we have only recently detected propylene oxide and still know very little about its origins. As part of my research I will use astronomical observations to better understand where and how propylene oxide forms. Together, these projects will greatly enhance our understanding of chiral molecules in the universe and shed light on one of the major questions in the study of the origins of life.

 

Jain, Ankit

Ankit Jain, Ph.D.
Education: Jawaharlal Nehru Centre for Advanced Scientific Research, Ph.D., Supramolecular Chemistry
Institution: Research Foundation of CUNY on behalf of Advanced Science Research Center (laboratory of Rein Ulijn)

Project: Searching peptide sequence space for prebiotic aggregates and catalysts

Origins of life lie primarily in the complex processes that simple molecules began to perform millions of years ago. These processes form the precursors for most vital biological functions in our now-evolved biochemistry. The catalytic action of enzymes, reproduction of cells and replication of our genetic matter — all of these vital processes — are believed to have simple origins. Recent papers suggest that short peptides can have a vital role to play in all of these processes from an origins-of-life perspective. However, from the huge library of peptide sequences that are possible, only a very small percentage has been screened for their utility in assisting the simple chemical precursor processes. This has been due to the fact that the only available alternative currently is the manual screening of a sequence, which is, of course, an arduous task.

We in this proposal try to alleviate this problem by designing a dynamic (constantly exchanging) library of peptides that will be engineered to respond to various chemical selection steps. Through these steps, the library should enrich a suitable candidate for a chemical transformation on its own. Dimers of various combinations of amino acids would form the initial feed, and the library would be under constant rearrangement for choosing the best combination out of these amino acids until it converges to a major product of a suitable candidate. This approach is novel, as covalent bonds between amino acids that form peptides are known to be inherently non-dynamic and, in the past, have been difficult to manipulate. Our approach uses the reversible enzymatic hydrolysis of this covalent bond to its advantage by converging the library to a suitable candidate. This candidate can further be isolated and tested independently for its efficacy in performing the desired chemical transformation. It should be noted that the feed of amino acid dimers will only consist of amino acids relevant to prebiotic chemistry so that the final product obtained can be used for relevant prebiotic investigations. Since the peptides are in dynamic exchange, the convergence of such a library can be affected by various screening steps.

In this proposal, we have chosen specific strategies so the screening can be suited for peptide catalysts that can either act as prebiotic enzyme mimics or can facilitate auto-reproduction of lipid vesicles or can act as binders for RNA and facilitate its non-enzymatic replication. Thus, from a common strategy, suitable peptide candidates can be selected by simply varying the screening steps. We believe that this approach would not only allow screening of a large portion of available prebiotic peptide sequence space, but will also serve as a common platform upon which prebiotic peptides relevant to important questions on origins of life — such as enzyme mimics, self-reproduction of lipid vesicles and non-enzymatic replication of RNA — can be developed.

 

Johnson, Alexandria

Alexandria Johnson, Ph.D.

Education: Purdue University, Ph.D., Atmospheric Sciences
Institution: Massachusetts Institute of Technology (laboratory of Daniel Cziczo)

Project: Clouds in Exoplanet Atmospheres – Are They Blocking our View of Life Below?

The identification and characterization of extra solar planets, or exoplanets, has given context to Earth and the potential for analogs orbiting other stars. However, one long-standing question remains – Can these planets sustain life as we know it? A first step in the search for life beyond our solar system is the detection of biosignature gases; known to be produced when Earth based life metabolizes. Yet a fundamental uncertainty remains in just how easily these gases can be detected through constituents in exoplanet atmospheres such as clouds.

In this project we will use theory and laboratory based experiments to determine how cloud particles interact with light across the visible spectrum and under a wide range of atmospheric compositions, pressures, and temperatures. The aim of this project is two fold. First, to better understand the role and properties of clouds in exoplanet atmospheres. Second, use of this information to determine how clouds will directly limit our ability to detect biosignature gases. We believe this work is critical for recognizing biosignatures in the very different environments on exoplanets and that cutting edge laboratory research on exoplanet atmospheres and clouds is the best way to approach this problem. The results of this work will aid with observations of exoplanet atmospheres and biosignatures through direct imaging or transmission spectroscopy, as well as exoplanet atmospheric and radiative balance models which can give valuable information on the surface habitability of exoplanets.

 

NachefClaudia El Nachef, Ph.D.

Education: University of Florida, Ph.D., Organic Chemistry
Institution: University of Ottawa (laboratory of André M. Beauchemin)

Project: Simple Aldehydes and Carbohydrates as Prebiotic Catalysts

Over decades, scientists have been trying to understand how life as we know it today emerged from simpler molecules. From a chemical evolution perspective, the molecular complexity of life is daunting. Building on the key Miller experiment, scientists have attempted to rationalize how simple molecular building blocks (HCN, NH3, CH4, aldehydes, etc.) have led to more complex structures such as: purines, pyrimidines, amino acids, and eventually to self replicating machinery. By definition, these structures must form through intermolecular reactions, for which there is an entropic penalty. Intermolecular reactions are also inherently slow at low concentrations. Catalysis of difficult intermolecular reactions is very important, as it could have dictated how chemical evolution occurred.

This proposal aims at investigating the roles of simple aldehydes and carbohydrates as catalysts in chemical evolution (prebiotic chemistry). An important goal is to establish that aldehydes could have acted as “simple enzymes” for many reactions involving water, which were crucial to form the building blocks of life (amino acids and base pairs). Second, it will show that these aldehydes can operate as catalysts under dilute aqueous conditions, through a pre-concentration mechanism that avoids most of the entropic penalty associated with intermolecular reactions. In parallel, studies will focus on possible mechanisms through which aldehydes and carbohydrates could have induced homochirality under prebiotic conditions, and create the single handedness observed in organic molecules. Overall, this work will establish that several prebiotic aldehydes and carbohydrates are “sweet” catalysts, thus addressing important void in the prebiotic chemistry literature.

 

raghav

Raghav Poudyal

Education: University of Missouri-Columbia, Ph.D., Biochemistry
Institution: The Pennsylvania State University (laboratory of Philip Bevilacqua)

Project: The RNA World inside compartments: A study of formation and functions

The RNA World hypothesis posits that Ribonucleic acid (RNA) molecules were among the primordial catalysts. Over the last two decades, many labs have isolated both natural and artificial catalytic RNAs through comparative genomics and in vitro selection experiments. While the catalytic repertoire of RNA is well established, the formation of these biopolymers and acquisition of functions by RNA molecules in prebiotic microenvironment are not well understood. Compartmentalization of molecules is ubiquitous in modern biology and certainly was very important during the early evolution of life to circumvent infinite dilution of functional molecules. Proposed work will study the conditions that favor both non-enzymatic and RNA catalyzed formation of RNA in novel coacervate compartments. We will also determine the effects of microenvironments and cosolutes in the activity and fitness landscape of the naturally occurring ribozyme. It has been shown previously that Magnesium (Mg2+), nucleotides and other molecules can partition at very high concentrations inside coacervates, thus favoring high activity of catalytic RNAs inside compartments. Through cutting-edge high throughput sequencing, changes in the local fitness landscapes of naturally occurring ribozyme will be determined and correlated to mechanistic studies obtained from classical biophysical techniques. This study will vastly increase our understanding of factors that influence formation of RNA and its ability to catalyze chemical reactions; both of which will have an enduring impact in the field of origins of life.

 

Paul Carroll

Sukrit Ranjan, Ph.D.
Education: Harvard University, Ph.D., Astronomy & Astrophysics
Institution: Massachusetts Institute of Technology (laboratory of Sara Seager Group)

Project: The UV Ultraviolet Environment for the Origin and Evolution of Life

We are in the midst of two revolutions in our understanding of life and its origins (abiogenesis). The first revolution is chemical: Long-standing problems in chemistry relating to the origin of life (prebiotic chemistry) are rapidly being solved. In the RNA world hypothesis, an abiotic synthesis of RNA is the key step in the origin of life, and the first plausibly prebiotic syntheses of RNA are now being discovered. The second revolution is astronomical: Recent studies have shown that potentially habitable planets orbiting other stars (exoplanets) are common, and the next generation of telescopes will be able to search them for evidence of life.

Ultraviolet (UV) light plays a key role in both of these revolutions. UV photons have the energy to power molecular and atomic transitions. This means that UV light can both harm nascent life and power the synthesis of prebiotically important molecules (e.g. RNA). Whether and how UV light helps or impedes the origin of life depends on the nature of the UV light that penetrates the atmosphere and reaches the planet’s surface. Consequently, it is critical to characterize the surface UV environment for prebiotic chemistry.

I propose three investigations to constrain the surface UV environment and explore the implications for prebiotic chemistry. The first investigation focuses on the UV environments for planets with highly scattering atmospheres, due to either high surface pressures or thick clouds. The second investigation focuses on the potential for elevated rates of volcanic outgassing, of the kind suggested for the young Earth and young Mars, to suppress UV light at the surface. The third investigation focuses on the impact of stellar flares, which are more common and more energetic for younger stars, on the surface UV environment. These investigations have applications both within the solar system (e.g., for the young Earth and young Mars) and outside it (e.g., for exoplanets).

This work will help prebiotic chemists understand whether UV-sensitive prebiotic chemistry discovered in the lab could work in nature, and the environmental context in which abiogenesis occurred. It will help astronomers understand whether life can emerge and endure on planets orbiting active stars, like Proxima Centauri b, our recently discovered potentially habitable nearest neighbor. This work will constrain which kinds of planets are the friendliest for the emergence of life, and hence which ones are the best targets for telescopic searches for extraterrestrial life. These searches will start in earnest in 2018 with the launch of the James Webb Space Telescope.

My proposed work is a novel investigation of the possible UV environments on planetary surfaces, critical for understanding both prebiotic chemistry on Earth and the habitability of extrasolar planets. It synergizes strongly with existing SCOL research initiatives and with work being done at my proposed host institution.

 

Sarah Rugheimer

Sarah Rugheimer, Ph.D.

Education: Harvard University, Ph.D., Astronomy and Astrophysics
Institution: University of St. Andrews (laboratory of Mark Claire)

Project: Modeling Atmospheres: Warming Archean Earth to Detecting Biosignatures

Atmospheric modeling allows us to examine two key areas of interest in origins research – the remote detection of life on an exoplanet and the atmospheric conditions of early Earth that gave rise to the origin of life. Theoretical modeling of atmospheres is essential in determining the size, resolution, and observing time required for a telescope to detect signs of life, or biosignatures, around an Earth-like planet orbiting a distant star. Currently all observing strategies for rocky planets rely on the ability to add multiple observations of a planet to detect atmospheric gases. This inherently assumes the planet’s atmosphere is constant in the months or years it takes for these multiple observations. However, stars can have variations in their output of high-energy light over that time. I propose to examine how the atmosphere might change due to this variation in high-energy light from the host star. I will then test how averaging multiple observations from a changing atmosphere might confuse our search for biosignatures in the future.

I also am interested in understanding the early Earth conditions that gave rise to the origin of life. We have geological evidence for warm climates and liquid water on the surface of Earth 4.4 billion years ago, yet it is difficult for current climate models to predict above freezing temperatures. This is called the Faint Young Sun Paradox. I propose to look at a potential solution to the paradox by including clouds in our climate model. In addition, a natural output of my models is the amount of high-energy light reaching the surface of a planet. This high-energy light can have both positive and negative effects on early life and chemistry. I propose to collaborate with other Simons teams to model the amount of high-energy light reaching the surface at the geological times of interest to them in their experiments.

 

Teresa Ruiz Herrero

Teresa Ruiz Herrero, Ph.D. 

Education: Autonomous University of Madrid, Ph.D., Soft Matter Physics
Institution: Harvard University (laboratory of Mahadevan Lakshminarayanan)

Project: Dynamics of growth and division in prebiotic vesicles

Self-replicating vesicles serve as a model for prebiotic cells, the precursors of life. These originated when a self-replicating biomolecule was separated from its environment by a permeable barrier able to grow and divide. This compartmentalization allowed for different chemical properties between the interior and the exterior media and eventually for specialization and competition between cells, which is the basis for Darwinian evolution. How these early cells could grow and divide without complex machinery remains an open question. The growth, shape and dynamics of these primitive vesicles can shed light on the ways modern cells have evolved by exploiting those characteristics to develop their replication mechanisms. Using a combination of theoretical and computational tools, we will investigate these questions with the aim of characterizing the conditions that allow these systems to replicate and evolve.

 

Stamenkovic,-Vlada_crop

Vlada Stamenkovic, Ph.D.

Education: University of Muenster, Ph.D., Earth, Atmospheric, and Planetary Sciences
Institution: California Institute of Technology (laboratories of Woodward W. Fischer and Joseph Kirschvink)

Project: Life From Inside Out: Connecting Geodynamics to the Origins of Life

All life we know occupies mostly the surface, oceans, and shallow crust of our planet – not reaching more than a few kilometers into the planet’s interior.

However, this inhabited environment is only a small part of our whole planet. The planet interior from rocky crust and mantle to the metallic core is the largest heat and nutrient reservoir that life can access. Tectonic forces and heat transport deep within the planet control what kind of nutrients reach the surface and what kind of nutrients are being removed from our atmosphere and oceans.

Therefore, the planet interior does significantly impact the origins of life and moreover all biogeochemical processes that determine the habitability of Earth and any rocky planet in our solar system and beyond.

In this proposal, I suggest to explore “Life from inside out”, or in other words the geodynamical connections to the origins of life. To achieve this goal, we must fully connect the interior evolution of planets with biogeochemical cycles occurring in oceans and on land. To get closer to this goal, the best approach is to 1) start exploring the geodynamically driven emergence of hydrogen, a first nutrient for life, as well as 2) to determine the potential of a geodynamic regulation of the atmospheric oxygen concentration, an element necessary for the emergence of complex life.

The oxygen and the hydrogen cycles are the key to explore the connections between planet interiors and the origins of life because oxygen and hydrogen significantly affect interior dynamics.

Answering both questions will allow us to explore the geodynamical drivers for the origin of life, to start uniting geodynamics with biogeochemistry, and to unveil whether or not Earth is a rare oasis for life in the Galaxy.

 

Rafałl Szabla

Rafał Szabla, Ph.D.
Education: Masaryk University, Ph.D., Biomolecular Chemistryes
Institution: Institute of Physics, Polish Academy of Sciences (laboratory of Andrzej Sobolewski)

Project: Mechanistic Studies of Prebiotically Plausible Ultraviolet-Induced Chemistry

Solar radiation could have played a crucial role during early chemical evolution, owing to the postulated higher sun activity in the ultraviolet (UV) spectral region and the absence of the ozone layer on the early Earth. The remarkable photostability of biomolecular building blocks and the recently discovered intrinsic self-repair mechanisms of oligonucleotides can be considered molecular fossils and support this hypothesis. UV irradiation is also an important source of energy, which often selectively promotes chemical reactions that would not be feasible otherwise. In this context, thorough understanding of prebiotically plausible UV-induced processes might play a fundamental role in studies that aim to discover the origins of biomolecules on Earth. High-level quantum chemical calculations are among the most accurate tools that help to determine the fates of UV-excited molecules. They can serve as a ‘molecular microscope’ and enable observations of the critical events in the photoreactivity. Such theoretical studies can be conducted both by statically probing the multidimensional space of molecular coordinates responsible for a specific photoreaction, or dynamically by tracking the molecular changes on a femtosecond timescale. It is important to mention that theoretical investigations of photochemical processes require particular care in appropriate method choice. This is mainly caused by the very complex nature of the electronic wave function that describes photoexcited molecules. Quantum chemistry was proved to solve many photochemical problems that could not be addressed by conventional experimental techniques. Furthermore, sophisticated time-resolved ultrafast spectroscopic experiments greatly benefit from the support provided by quantum chemistry; for instance, in interpretation of the spectra. In this project, I will apply state-of-the-art quantum chemical methods in order to investigate the mechanisms of prebiotically plausible photoinduced reactions. In addition, I will study the intrinsic UV-induced self-repair mechanisms occurring in nucleic acid strands to answer the question of whether strong UV fluxes could have affected the preselection of DNA sequences. These theoretical investigations, performed in close collaboration with several experimental laboratories, could provide many fundamental insights into the role of UV irradiation during the early stages of abiogenesis.

 

Stephanie Valleau

Stephanie Valleau, Ph.D.

Education: Harvard University, Ph.D., Chemical Physics
Institution: Stanford University (laboratory of Todd J. Martinez)

Project: Atomistic exploration of abiogenesis with a nanoreactor

In this project, we aim to understand how life-essential molecules were formed using a theoretical lens. We will investigate how atoms and molecules could have combined in the presence of carbon-nitrogen and sulfur compounds to produce the fundamental building blocks of life: amino acids, nucleotides and lipids. This will be carried out on video cards and large computer clusters using the laws of classical and quantum mechanics to follow the movement of all atoms. We will define a bubble of life containing the initial molecules in a specific environment, for instance in a water pool. The compounds will interact and collide, bonds will be broken and new bonds formed. Hundreds of picoseconds later we will examine what has been created. We will look at the time-dependent evolution of this bubble to find intermediate structures and determine how fast the whole process occurred. We will also investigate the influence of external factors such as temperature and pressure and whether adding/removing specific compounds strongly influences the reactions. Ultimately we will see whether the products can combine to form long chains, the ancestors and precursors of RNA.

 

Wang, Xingchen

Xingchen Wang, Ph.D.

Education: Princeton University, Ph.D., Geosciences
Institution: California Institute of Technology (laboratories of Alex Sessions, Woodward Fischer and Jess Adkins)

Project: N isotopes in stromatolites: Linking the N cycle to the origins of life

Nitrogen is a key element of life and its availability on the early Earth played a crucial role in the origins and expansion of life. Although nitrogen is abundant in the atmosphere in the form of dinitrogen, only specialized organisms that express a nitrogenase enzyme (‘nitrogen fixers’) can break the triple bonds of dinitrogen and use them as a nitrogen source for growth. In the modern oceans, the entire ecosystem is sustained by the nitrogen fixed by nitrogen fixers and its later recycling. Thus, the appearance of nitrogenase on the early Earth would have been critical for sustaining the earliest biosphere. However, the evolutionary timing and type of the first nitrogenase are widely debated, primarily because we lack reliable proxy data from the earliest rocks. Natural variations in the ratio of the two stable nitrogen isotopes (14-N and 15-N) recorded in fossil stromatolites (one of the earliest fossils) could provide a useful means to addressing these questions, because nitrogenases alter their relative abundance in predictable ways. Thus far, however, analytical techniques have targeted nitrogen isolated from bulk rocks and raise concerns about how well this measurement represents original organic matter. This proposal aims to apply a novel technique that I developed during my Ph.D. to measure nitrogen isotopes in organic nitrogen protected by carbonate minerals, which should provide a more robust record. My proposed study of nitrogen isotopes in fossil stromatolites should help constrain the evolutionary timing and type of the first nitrogenase.

 

Wang, Yajun

Yajun Wang, Ph.D.
Education: University of British Columbia, Ph.D., Nucleic Acid Chemistry
Institution: University of California, Irvine (laboratory of John Chaput)

Project: Evaluating TNA as a Pre-RNA World Catalyst

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are nature’s solution to the problem of how to store and transfer genetic information between members of the same species. In addition, certain RNAs are also able to catalyze reactions that involve such complex chemistry as RNA processing and protein synthesis. RNA’s ability to be a genetic material and biocatalyst led to the RNA world hypothesis, which suggests that modern life evolved from RNA-based life forms in which RNA stored genetic information and catalyzed chemical reactions. Despite the importance of RNA in modern biology, it is not clear if RNA was the first genetic material of life or an evolutionary intermediate that gave rise to modern life.

One could imagine that whatever chemistry gave rise to RNA would have produced other RNA analogs, some of which could have competed with or possibly even preceded RNA in the evolution of life. One interesting candidate for an RNA progenitor is threose nucleic acid (TNA), which is able to exchange information with RNA by forming complementary A-T and G-C pairs in a Watson–Crick double helix. Demonstrating that TNA can catalyze chemical reactions in the same way as RNA would help advance the theory that TNA is a viable RNA world progenitor. This project will use Darwinian evolution methods to evolve a TNA enzyme for a chemical reaction, so a direct comparison can be made between the functional properties of RNA and TNA.

 

Zeng, Li

Li Zeng

Education: Harvard University, Ph.D., Astronomy and Astrophysics
Institution: Harvard University (laboratory of Stein Jacobson)

Project: Uncovering the Chemistry of Earth-like Planets

We propose to use evidence from our solar system to understand exoplanets, and in particular, to predict their surface chemistry and thereby the possibility of life.

An Earth-like planet, born from the same nebula as its host star, is composed primarily of silicate rocks and an iron-nickel metal core, and depleted in volatile content in a systematic manner. The more volatile (easier to vaporize or dissociate into gas form) an element is in an Earth-like planet, the more depleted the element is compared to its host star.

After depletion, an Earth-like planet would go through the process of core formation due to heat from radioactive decay and collisions. Core formation depletes a planet’s rocky mantle of siderophile (iron-loving) elements, in addition to the volatile depletion.

After that, Earth-like planets likely accrete some volatile-rich materials, called “late veneer”. The late veneer could be essential to the origins of life on Earth and Earth-like planets, as it also delivers the volatiles such as nitrogen, sulfur, carbon and water to the planet’s surface, which are crucial for life to occur. These volatiles would be lost in the earlier stages (volatile depletion and core formation), rendering them absent on the planet’s surface, until delivered later when the planet’s surface cooled down enough to retain them.

Finally, the materials delivered to the surface of the planet would be gradually mixed into the planet’s mantle through mantle convection.

By parameterizing and modeling each of these steps properly, we plan to build an integrative model of Earth-like planets from the bottom up. We would like to infer their chemical compositions from their mass-radius relations and their host stars’ elemental abundances, and understand the origins of volatile contents (especially water) on their surfaces, and thereby shed light on the origins of life on them.

 

Past Fellows

 

BellColorPhot_crop

Elizabeth Bell, Ph.D.

Education: University of California, Los Angeles, Ph.D. Geochemistry
Institution: University of California, Los Angeles, Earth and Space Sciences (laboratory of Mark Harrison)

Project: A Search for Isotopic Traces of Life in 4.0 to 4.4-Billion-Year-Old Minerals

Because Earth’s surface is continually scoured by water and other agents of erosion, our geologic record becomes increasingly sparse with age. Although the planet is over 4.5 billion years (Ga) old, rocks older than 4 Ga are currently unknown. This makes the earliest history of Earth, and any possible biosphere older than 4 billion years, largely inaccessible.

However, tiny grains of the mineral zircon (approximately the width of a human hair) from the Jack Hills in Western Australia range as old as 4.4 Ga, constituting the oldest known materials on the planet. These zircons contain abundant inclusions of earlier minerals, some of them carbon-bearing, that were enclosed in the zircon during its formation.

Since biologically-derived carbon tends to have characteristically low ratios of the isotope C-13 compared to C-12, carbon isotope ratios can be proxies for the presence of life even when direct fossils are not available. Bell intends to analyze a significant number of carbon-bearing inclusions in Jack Hills zircons in order to constrain the over-4-Ga carbon isotope record and determine whether it is consistent with the presence of life. This would constitute the oldest known evidence of life on Earth.

 

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Ziwei Liu, Ph.D.

Education: State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Ph.D. Inorganic Chemistry
Institution: University Montpellier, Institut des Biomolécules Max Mousseron (laboratory of Robert Pascal)

Project: Coevolution of RNA and Peptides — Connecting the Activation Processes

The observation that amino acids are easily available in abiotic environments suggests that RNA coevolved with peptides in an RNA world. In other words, the carriers of information may have coexisted with short polymers of amino acids built by chemical pathways predating the translation of nucleic acid sequences into proteins. This possibility makes the subsequent transition to an RNA-protein world logical.

Ziwei Liu’s work is aimed at precisely identifying chemical pathways potentially responsible for the connection of peptide and RNA chemistries. The present-day biosynthesis of peptides, through elongation of peptide chains by the stepwise addition of activated amino acids in the ribosome, was probably preceded by simpler chemical processes involving activated amino acid building blocks and adducts with short RNA strands.

Beginning with previous work in his advisor’s lab, which showed that intermediates made of amino acid and nucleotide moieties can be easily formed, Liu will work to enlarge the scope of the process to the formation of peptide chains connected to simple nucleotides.

He will study the chemical and kinetic properties of these activated intermediates for their role in the elongations of both peptides and nucleotides. He will also study the stereochemistry of the reactions as a potential process leading to mirror symmetry breaking.

These investigations are part of an ongoing research program based on the physicochemical view that self-organization in the emergence of life process requires both a far-from-equilibrium state and the replication of chemical entities. Introducing free energy through activated amino acid monomers or activated peptides as a means to drive the replication of an information support and the selection of the more efficient sequences may thus be considered an essential step in the evolutionary process leading to life.

 

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Irena Mamajanov, Ph.D.

Education: Brandeis University, Ph.D. Physical Chemistry
Institution: Carnegie Institution of Washington, Geophysical Laboratory (laboratory of George D. Cody)

Project: Potential Protoenzymes: Structure and Function of Hyperbranched Polyesters

Enzymes are biopolymers responsible for the catalysis of chemical conformations that sustain life. Modern enzymes are comprised of complex protein or RNA structures unlikely to be present on prebiotic Earth. Enzymatic molecules through tree-dimensional folding create compartments that bind and orient specific reactions. Moreover, enzymes can create local environments with polarity different from water to augment the reaction rate. These properties of enzymes can be approximated by synthetically accessible polymers.

One such class of macromolecules is hyperbranched polymers, structures with a high degree of branching that possess globular structures similar to biological enzymes. Mamajanov will study the formation, structure and catalytic properties of hyperbranched polymers under prebiotically plausible conditions. A successful experimental demonstration of such approach would provide a valuable model of how the first enzyme-like systems could have arisen on Earth.

 

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James Saenz, Ph.D.

Education: Massachusetts Institute of Technology, Ph.D., Chemical Oceanography
Institution: Max-Planck-Institut fuer Molekulare Zellbiologie u. Genetik (laboratory of Tony Hyman)

Project: The Emergence and Evolution of Molecular Order in the Cell Membrane

One of the most interesting and elusive problems in science has been to understand how life emerged on earth. This is intricately linked to the question: How did the first cells arise? Modern life employs a complex and highly interconnected chemical system to assemble its parts and replicate. However, life did not start with these advanced biochemical tools and would have relied on simple systems that 1) could self assemble from preexisting molecules available on early Earth and 2) segregate biomolecules from the environment by some means of compartmentalization. Encapsulation by lipid membranes is one mechanism to compartmentalize primitive biomolecules.

In the scope of this proposal I want to ask: what were the early Earth membranes like? Membranes are thought to have emerged from the self-assembly of primitive lipids that were present on early Earth. The properties of early membranes would have been dependent on the structure of these primitive lipids. Over time, evolution would then have selected more specialized membrane compositions ultimately leading to the first cellular membranes. In this context, the interactions between membranes and early biomolecules (e.g. RNA) may even have served as a primitive form of heredity before a formalized genetic code emerged.

I will examine the properties of membranes that could have emerged from potential early Earth lipids. In particular I will test how aromatic hydocarbons that are thought to have been present on early Earth can modulate the thermodynamic order of membrane lipids. I will approach this through a comprehensive range of classical and modern biophysical tools in model membrane systems aimed at mimicking the complexity of primitive membranes.

By understanding the potential distribution of properties of primitive membranes, I aim to excavate the fundamental principles that allowed life to emerge, bringing us closer to understanding how modern membranes function and how to engineer functional membranes from the bottom up.

 

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Kartik Temburnikar, Ph.D.

Education: University of Maryland, Baltimore County, Ph.D. Organic Chemistry
Institution: Arizona State University, the Biodesign Institute (laboratory of John C. Chaput)

Project: Investigating TNA as a Candidate RNA Progenitor

The RNA world hypothesis postulates that cellular life based on DNA genomes
and protein enzymes was preceded in evolutionary history by RNA-based life forms that stored information and catalyzed chemical reactions. This hypothesis is supported by many lines of evidence, including the existence of RNA enzymes in nature.

Whether RNA was the first genetic material of life or an important evolutionary intermediate is not yet known. Problems associated with the prebiotic synthesis of ribose and non-enzymatic replication of RNA suggest that simpler genetic polymers whose structures were more accessible on the early Earth may have preceded RNA.

One possible candidate is threose nucleic acid, or TNA. TNA is a synthetic genetic polymer that contains a four-carbon threose sugar in place of nature’s five-carbon ribose sugar found in RNA. TNA is an attractive candidate for an RNA progenitor, because threose is chemically much simpler than ribose, and TNA can exchange genetic information with RNA. This latter observation provides a plausible mechanism for passing information between successive genetic systems. In addition to information storage and chemical simplicity, early genetic polymers would have also needed to fold into shapes with catalytic activity.

Kartik Temburnikar aims to explore the functional properties of TNA as an RNA progenitor by evolving a TNA enzyme capable of joining two strands of TNA together to form longer TNA polymers. If successful, this template-copying reaction will provide new insights into mechanisms that could have given rise to early self-replicating genetic polymers.

 

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Falk Wachowius, Ph.D.

Education: Max Planck Institute for Biophysical Chemistry, Göttingen, Ph.D. Nucleic Acid Chemistry
Institution: Medical Research Council Laboratory of Molecular Biology (laboratory of Philipp Holliger)

Project: An RNA Polymerase Ribozyme With General Replication Capacity

One of the fundamental traits of life is self-replication. Therefore, the emergence of self-replication is closely linked to the origins of life itself. Several strands of compelling evidence strongly suggest that our current biology, which relies on DNA for information storage and proteins for catalysis, was preceded by a primordial biology that instead relied on DNA’s close chemical cousin, RNA, for both heredity and metabolism.

It is therefore widely believed that this ancestral biology, also referred to as the ‘RNA world’ began with an RNA molecule that acquired a capacity for self-replication and mutation and hence evolution towards ever more efficient self-replication.

Unfortunately, this primordial replicase appears to have been lost. However, we can reconstruct modern analogues and study the properties of these molecular ‘doppelgängers’ in order to better understand life’s first genetic system. Furthermore, using methods of evolution in the laboratory, we can retrace the first steps that this ancestral molecule must have taken and ultimately reconstruct an RNA world in the test-tube.

 

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Rui Wang, Ph.D.
Education: Shanghai Institute of Organic Chemistry, Ph.D., Organic Chemistry
Institution: Research Foundation of SUNY – University at Albany (laboratory of Jia Sheng)

Project: Evolutionary Roles of RNA Aptamers in the Origin of Biological Catalysis

Most of chemical reactions in the current biological systems are catalyzed by enzymes, which can bind, orient and activate the substrates in specific ways. While these functions are highly integrated in enzyme systems, they could be separated as different modules in the prebiotic chemistry. Based on the RNA world hypothesis, RNA evolved first as both genetic information carrier and catalyst before DNA and protein. Therefore, studying the evolutionary roles of RNA in small molecule binding, orientating and activating will provide new insights to explain the origins of biological catalysis as well as certain metabolic networks in the prebiotic chemistry.

The major hypothesis of this project is: small RNA aptamers, which may exist in different variants (such as the hybrid forms of 2’-5’-linked, deoxyribo- and threose linked RNAs), could play important roles by binding substrates with diversified modes, therefore channeling their reactivity towards the most useful products as the potential metabolites. In other words, perhaps early protocells relied on the ambient chemistry for their sources of materials, but simple aptamers, instead of the structurally more complicated ribozymes, helped things along by making the chemistry proceed in a more specific manner, resulting in higher yields of the desired materials, which might facilitate the early metabolisms. Although they might have been inefficient, these aptamers might be able to gradually evolve into a special catalyst of the desired reaction, perhaps by docking into certain relatively nonspecific ribozyme domains and cooperating with other auxiliary domains, similar as the example of ribosome that could evolve by the docking of peptidyl-transferring ribozymes into the protein frames.

In this proposal, we will use phosphorylation, a universal and critical metabolic step in the extant biological systems, as the study model to explore the effects of aptamers in the regioselective phosphorylation of purine and pyrimidine nucleosides, as well as some amino acids, small peptides and other metabolites.

 

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Dmitry Zubarev, Ph.D.

Education: Utah State University, Ph.D. Physical Chemistry
Institution: Harvard University, Chemistry and Chemical Biology (laboratory of Alán Aspuru-Guzik)

Project: Prebiotic Atlas: Exhaustive Exploration of Prebiotic Chemical Space

Advances in the investigation of the origins of life are associated with answers to the question: ‘Who was first?’ For example, we discuss which evolved first: metabolism, pre-RNA, RNA or DNA worlds. It is unclear to what extent chemistry of biological systems can be used to reconstruct early chemistries. This consideration makes it equally important to know: ‘What was there at all?’

The goal of Dmitry Zubarev’s research is to answer the latter question by using theoretical and computational approaches of the material design field to create a prebiotic atlas — a vast collection of reaction networks that cover prebiotic chemical space.

Zubarev will survey chemistries along the few known routes that connect simple molecules to biochemical systems. This will help to identify new routes and continue expansion into uncharted territories of the prebiotic world. The prebiotic chemical maps assembled into an atlas will be made available to scientists and the general public via Web interface with built-in research and educational tools.