Chemical Origins of Life

Since the 1953 experiment by Stanley Miller and Harold Urey, we have known that a mixture of simple gases of a primitive early-Earth atmosphere (water vapor, methane, ammonia, hydrogen) could be catalyzed to produce amino acids, the building blocks of life. But possible further steps, where amino acids join to form peptides or proteins with primitive functions are unknown. We have shown how different environmental conditions of pH, heat, and drying can promote the formation of different strings of amino acids (peptides), a step toward linking synthesis environment to the emergence of molecular information (Sibilska, 2018). Others have suggested how short peptides could interact to serve as information or replication templates, related to amyloid formation in neurodegenerative process that are linked to Alzheimers or Huntington’s disease. Meanwhile, clever biochemists have figured out ways to engineer peptides that can perform feats of self-replication. But it remains a wide-open challenge how a de novo wet-lab system, starting with amino acids, simple activating agents, and interfaces (solid-liquid or liquid-liquid) surfaces can give rise to any form of self-replication.

Peptides of glycine and alanine form over 24 hours of incubation, depending on whether activator (TP) is present or absent, the pH, and the temperature. (A) detected distribution of each species for temperatures 0-to100C (y axis) and pH 1-to-12 in the absence (black square) or presence (blue fill) of TP activator. The concentration of each […]

To understand in greater depth how different peptide products enrich, we studied how glycine(G) alone forms products of different length (GG, GGG, and GGGG) during sample drying. In (a) we see the how drying of 1 ml reaction solution is complete in about 8 hours (shaded box). In the presence of TP and at high […]

In the first step, at elevated pH and in the presence of trimetaphosphate (TP), glycine is activated at its N-terminus, and the activated glycine then reacts with glycine to form diglycine (GG), while generating protons that drive the pH down, as in Mechanism 1 (a). In the second step, at lower pH, diglycine or longer […]

The Human Virome in Health and Disease

The term, microbiome, describes the collective microbes that inhibit our bodies and other environments. In the Yin Lab we focus on a subset of the microbiome, the virome, or collective viruses associated with humans and their environments. Some viruses might be beneficial; for example, viruses that infect pathogenic microbes may contribute to a microbiome that promotes our health. Other viruses, especially the ones that make us sick, are well known, for example, HIV-1, hepatitis, ebola, the common cold, zika, and influenza. More recently, the COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2.

Many viruses, including coronaviruses, make errors when they reproduce by introducing mutations in their genomes. Such mutations can expand their powers, enabling them to infect new host species, like jumping from bats to humans. Or the mutant viruses can evade host immune responses and escape drug treatments. More broadly, the mutations can lead to diseases that persist or re-emerge.

Alternatively, extreme errors can delete key virus functions, rendering the virus non-infectious. Such ‘dead’ viruses are ubiquitous byproducts of virus infections in humans and in natural host reservoirs. Remarkably, such dead viruses can spring to life if they invade a productively infected host cell, where they can reproduce at the expense of the normal virus. These molecular parasites of normal virus growth have potential as therapeutics. It is currently unknown to what extent such defective viruses might stimulate host immune responses in ways that might be protective versus causing more severe disease. In the Yin Lab we are working to understand how such defective viruses can impact disease severity and how they might be engineered to prevent future pandemics.

To address this question, consider the delay time that describes how long it will take, following the start of infection, for virus progeny to be released from infected cells (left). Analysis of such growth curves for more than 100 viruses indicate delay times from less than 100 to more than 10,000 minutes or about 1 […]

Different cells from the same environment produce a wide range of virus particles from less than 100 (curve B3) to nearly 10,000 (curve C7 and A3); experiments are for vesicular stomatitis virus (VSV) infections of BHK21 host cells.  For details see Timm and Yin (2012).

When a virus infects a living cell, how long before virus progeny are released, and how many particles will be made? One may build a model for infection by writing equations that describe each of the essential steps: entry, transcription, translation, genome replication, particle assembly and release from the cell. Experimental data are used to […]

In the absence of interfering particles, virus infections spread uniformly to greater radii (far left, red protein expression linked to virus growth). When interfering particles are present, infection is limited (only patchy red). Green protein expression is driven by interfering particles, and yellow reflects a balance of co-infection (virus and interfering particles). For details, see […]

In the absence of flow regions of cell infection are localized (white points). But in the presence of outward radial flows, regions of infection are spread in the direction of flow (white comets). Culture wells are 35mm in diameter. Details are Zhu et al. 2007. How do spontaneous fluid flows arise in culture wells? Evaporation […]

Human Physiology

In the healthy human, diverse organ systems take up and distribute oxygen, digest food for energy, and rid the body of waste. Such systems are coordinated in part by the nervous system, which senses, transmits, and reacts to chemical and electrical signals throughout the body. But as individuals age, their physiological functions can decline. For example, 60% of adults over 40 suffer symptoms of the lower urinary tract, which include a need to urinate that may be frequent, urgent, or at night. Methods of nerve stimulation have potential to treat such symptoms, but nerve signaling from and to the bladder and urethra, while measurable, are not yet understood well enough to guide treatment.

In the Yin Lab we are part of a multi-disciplinary team to advance hybrid mechanistic-and-neural-network computational models of lower urinary tract function guided by wet-lab experiments on rats. As chemical engineers, we are applying principles of dimensional analysis to enable scale-up of results from rats to humans. At the same time, we are pioneering hybrid models that combine the benefits of mechanistic understanding with emerging data-driven methods.

  • In our cross-disciplinary study of the lower urinary tract, we reviewed the literature, highlighting how fluid flows and bio-mechanical signals share information with the nervous system. Our current efforts are advancing hybrid mechanistic-neural network models, informed by experimental rat data. The greatest gap in our understanding in the interface of the bladder-and-urethra with the nervous […]