The molpigs Podcast

molpigs

Welcome to molpigs, the Molecular Programming Interest Group! molpigs is a group aimed at PhD students and early career researchers within the fields of Molecular Programming, DNA Computing, and other related specialties. We run most of our events in the form of podcasts, which you can find right here!

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Brenda Rubenstein: Storage and Computing with Small Molecules: A Tutorial
12-11-2020
Brenda Rubenstein: Storage and Computing with Small Molecules: A Tutorial
For our first event, Brenda Rubenstein has presented a tutorial on her lab's approach to storage and computation, making use of the chemical properties of a variety of types of small molecules. This was a real tour-de-force, and is worth a watch. Be sure to listen to our subsequent Q&A session in a couple episodes time! Abstract: As transistors near the size of molecules, computer engineers are increasingly finding themselves asking a once idle question: how can we store information in and compute using chemistry? While molecular storage and computation have traditionally leveraged the sequence diversity of polymers such as DNA, our team has recently demonstrated that vast amounts of information can also be stored in unordered mixtures of small molecules. In this tutorial, I will begin by explaining this new, more general molecular storage paradigm and how polymers fit into it. I will then describe how our team has married combinatorial chemical synthesis with high resolution spectrometry to experimentally realize this paradigm and store GBs of information in small molecules and metabolites. Lastly, I will end with a discussion of how these storage principles can be combined with machine learning techniques to realize fully molecular neural networks for pattern recognition and image processing. The new paradigm discussed in this tutorial will lend itself to new means of increasing molecular storage capacity and interpreting the many small molecule chemistries that underlie "computing" within the body. ---Find more information at the episode page here:
Brenda Rubenstein: Storage and Computing with Small Molecules: A Tutorial
12-11-2020
Brenda Rubenstein: Storage and Computing with Small Molecules: A Tutorial
For our first event, Brenda Rubenstein has presented a tutorial on her lab's approach to storage and computation, making use of the chemical properties of a variety of types of small molecules. This was a real tour-de-force, and is worth a watch. Be sure to listen to our subsequent Q&A session in a couple episodes time! Abstract: As transistors near the size of molecules, computer engineers are increasingly finding themselves asking a once idle question: how can we store information in and compute using chemistry? While molecular storage and computation have traditionally leveraged the sequence diversity of polymers such as DNA, our team has recently demonstrated that vast amounts of information can also be stored in unordered mixtures of small molecules. In this tutorial, I will begin by explaining this new, more general molecular storage paradigm and how polymers fit into it. I will then describe how our team has married combinatorial chemical synthesis with high resolution spectrometry to experimentally realize this paradigm and store GBs of information in small molecules and metabolites. Lastly, I will end with a discussion of how these storage principles can be combined with machine learning techniques to realize fully molecular neural networks for pattern recognition and image processing. The new paradigm discussed in this tutorial will lend itself to new means of increasing molecular storage capacity and interpreting the many small molecule chemistries that underlie "computing" within the body. ---Find more information at the episode page here:
Dominic Scalise
04-12-2020
Dominic Scalise
Join us for the first of our ‘Lab Pigs’ series, in which we talk with early career researchers on their research and journey within our field. In this episode, we chatted with Dominic Scalise. We talked a lot with Dominic about his work towards building a stored program chemical computer. Dominic Scalise is a postdoctoral scholar in Lulu Qian’s lab at Caltech. He earned his PhD in chemical and biomolecular engineering from Johns Hopkins, advised by Rebecca Schulman, and his B.S. in mechanical engineering from UC Berkeley. His work focuses on developing a stored program chemical computer, and powering circuits using DNA buffer reactions. Abstract: Molecular programming extends computer science beyond electronics into chemistry, and lets humans directly program physical matter. However, chemical circuits remain arduous to program, often requiring months or years to design, implement, and debug even a single program. In stark contrast, we program modern electronics with much less effort. A critical step in simplifying electronic programming was the invention of “software” in the 1940s. I will outline how similar concepts of “chemical software”, in which programs are stored in memory rather than hard coded into the connections of chemical reaction networks, could dramatically simplify the task of chemical programming. I will then discuss some reaction motifs in development which may be useful for implementing chemical software. In this podcast, we found out that current chemical computers are just like the electronic computers from the 1940s, in that a computer program requires rewiring the hardware. They are small in size, error-prone, and take a long time to build. A stored program chemical computer may tackle these problems by being a robust universal circuit capable of running arbitrary algorithms, with the exact algorithm of a given computation depending on which instructions (software) are given. Dominic then discussed his approach—building a chemical memory and then a chemical processor, possible challenges in doing so, and his vision for the future. We also talked a bit about his experiences in academia. Dominic made a special announcement for molpigs members at the end about a grassroots project: a Molecular Programming textbook to drive the field through a collaborative approach. Stay tuned on our newsletter for more information! ---Find more information at the episode page here:
Tom Ouldridge: Molecular Programming and the Physics of Computation
09-01-2021
Tom Ouldridge: Molecular Programming and the Physics of Computation
Join us this week for a long and interesting conversation with Tom Ouldridge of Imperial College London on Maxwell’s demon, Szilard’s engine, what people get wrong about thermodynamics and information theory, how this all relates to biology, and how his lab is using these ideas to develop exciting new approaches to molecular programming. Tom Ouldridge is a Royal Society University Research Fellow in the Bioengineering Department, where he leads the “Principles of Biomolecular Systems” group. His group probes the fundamental principles underlying complex biochemical systems through theoretical modelling, simulation and experiment. In particular, they focus on the interplay between the detailed biochemistry and the overall output of a process such as sensing, replication or self-assembly. They are inspired by natural systems, and aim to explore the possibilities of engineering artificial analogs. We start by discussing Maxwell’s demon and Szilard’s engine—thought experiments from the 19th and early 20th centuries about the interplay of thermodynamics and information-processing. These have long captured the imagination of theoretical physicists. There is renewed interest in these thought experiments due our increasing ability to control systems at the molecular level. Many still disagree about the interpretation of these ideas, the implications for the second law of thermodynamics, and the consequences for thermodynamics of computation. Szilard’s engine is a simpler version of Maxwell’s thought experiment, but which is mathematically tractable, considering only a single particle separated by a divider attached to a weight. If the particle and the weight are on the same side, then the particle can bounce against the divider and lift the weight, doing work. By resetting the divider, this step can be repeated to extract more work. Tom talks about how this seeming paradox may be resolved. Tom discusses how his group has implemented a theoretical Szilard engine in biomolecules; by explicitly rendering each step of the engine as a biochemical process (using cell surface receptors). This helps demystify the whole process by rendering all “information theoretic” steps as concrete, real, processes. Doing so is helpful not only in resolving old thought experiments, but because the crucial idea—that the generation of correlation between non-interacting degrees of freedom is thermodynamically costly—is of fundamental significance to natural and synthetic molecular information-processing systems. ---Find more information at the episode page here:
Erik Poppleton
28-02-2021
Erik Poppleton
In the third episode of our ‘Lab Pigs’ series, which highlights the research and journeys of early career researchers in our field, we talked with Erik Poppleton, of the Biodesign Institute at Arizona State University. Erik researches the use of computational modeling in informing the design of molecular machines. As part of this, he also develops general-use analysis tools for oxDNA, and conversion tools to integrate the various design and simulation tools in the nucleic acid nanotechnology ecosystem. We talked about his research, his experience writing academic software, and the relationship between geology and molecular programming. Core Simulation Tools- Main oxDNA documentation: Current stable release (being retired soon): Bleeding edge release (has Python bindings!): The model is also available as part of LAMMPS, documentation can be found here: tutorials- A textbook chapter covering how to relax and simulate origamis: A textbook chapter covering the details of molecular simulation: Example input files: tools- TacoxDNA, converters from design software to oxDNA: oxView, a visualizer and editor for oxDNA: oxView documentation: oxdna_analysis_tools, a library of python scripts for basic simulation analysis: oxdna.org, a public webserver for running simulations: oxdna.org- ox-serve, run interactive simulations in your web browser using a Google Colab GPU: course, if you find these tools useful, please remember to cite us! The citations for each tool can be found in its documentation (oxdna.org paper coming soon!) ---Find more information at the episode page here:
Kate Adamala
24-03-2021
Kate Adamala
Kate Adamala is a biochemist building synthetic cells at the University of Minnesota College of Biological Sciences. Her research aims at understanding chemical principles of biology, using artificial cells to create new tools for bioengineering, drug development, and basic research. The interests of her lab span questions from the origin and earliest evolution of life, using synthetic biology to colonize space, to the future of biotechnology and medicine. She received a MSc in chemistry from the University of Warsaw, Poland, studying synthetic organic chemistry. In grad school, she worked with professor Pier Luigi Luisi from University Roma Tre and Jack Szostak from Harvard University. She studied RNA biophysics, small peptide catalysis and liposome dynamics, in an effort to build a chemical system capable of Darwinian evolution. Kate’s postdoctoral work in Ed Boyden’s Synthetic Neurobiology group at MIT focused on developing novel methods for multiplex control and readout of mammalian cells. Her full first name spells Katarzyna; she goes by Kate for the benefit of friends speaking less consonant-enriched languages. First we discuss Kate’s synthetic cells and whether or not they are living. These are phospholipid liposomes which encapsulate a full central dogma (transcription, translation). Synthetic cells are more complex than biochemical experiments, but at the moment, Kate does not consider her synthetic cells living. These cells are not self replicating, currently requiring a graduate-assisted replication. We then have an extended discussion about the ribosome, why it’s the biggest hurdle to achieving true self replication, and why it kind of sucks as a catalyst! Next, we move on to how synthetic cells can be used to aid in the research of brain computer interfaces (BCI). Kate’s vision is that, because synthetic cells can be so robustly controlled, they represent a form of “programmable goo” which would interface much more robustly with our brains than traditional silicon. She envisions the role of synthetic cells as being used as a less injurious interface for BCIs, which currently cause significant scarring to the brain. Finally, we talk about one of the most interesting topics covered on the molpigs podcast: space exploration! Kate discusses how synthetic cells, being so programmable, might be ideal devices for Martian terraforming. By engineering poly-extremophiles (extremophiles which are robust to many extreme conditions, organisms which do not exist on Earth) specific to the environment of Mars, it may be possible to design a metabolism capable to transforming Martian soil into something fertile. Additionally, synthetic cells might be used as on-board biochemical printers on long space missions. Their programmable metabolism may enable us to produce any biomolecule, such as medicines on demand. ---Find more information at the episode page here:
Namita Sarraf
27-03-2021
Namita Sarraf
What do ant colonies have to do with molecular programming? In this podcast, we spoke with Namita Sarraf, a graduate student at Caltech in Lulu Qian’s group. We discuss her research, which revolves around the production of multifunctional and modular DNA robots. Namita takes inspiration from ant colony dynamics to design robots, which alone may exhibit simple behaviour, but show emergent complexity when put together. By having these robots pattern the surface, ant pheromones can be emulated. One task which these “DNA ants” are being made to perform is maze-solving. Because traditional methods are not ideal for DNA robots, Namita is developing bespoke maze-solving algorithms. As she points out however, maze-solving by itself is not inherently useful, and for this reason these DNA robots are being built for modularity and composability. By combining maze-solving with cargo sorting Namita can generate more complex behaviours with real world applications. We then move on to talk about how Namita moved into molecular programming from her original field of tissue engineering. We discuss graduate student life, impostor syndrome, and the generation of negative results and their use in publishing. Namita is also one of the founders of the open collaborative textbook project “The Art of Molecular Programming”, a grassroots project aimed at collecting experts in the field to build a comprehensive textbook which will serve as a starting point for new and existing researchers. We discuss how the idea came about, inspired by the spirit of the Synthetic Biology community. The Art of Molecular Programming aims to be a project which collects all of the useful pieces of lore which exist scattered throughout the molecular programming literature and put them in one useful repository, taking away the pain that new graduate students endure in their first years while they struggle to build up a coherent picture of the field by reading countless ad-hoc papers. ---Find more information at the episode page here:
Kent Kemmish
16-05-2021
Kent Kemmish
Join us this week for an extremely interesting conversation with Kent Kemmish, the founder and chief exorcist (yes, exorcist) officer of Molecular Reality, and the creator of the new, and world’s first “molecular” games console, the demonpore 64. This is our first podcast with a member of the molecular programming community who works in industry, and in the startup sector. At its heart, Kent’s demonpore 64 is a device which utilises solid state nanopores in order to sense its environment at the molecular level. Kent and his team have reduced the cost to manufacture this traditionally lab based and expensive equipment by orders of magnitude. Kent’s hope is that by making this technology cheap, accessible and gamified, gamers can engage in science and data collection on behalf of scientists. This ought to enable scientists to perform very very large experiments, which would otherwise be impossible. We discuss what a molecular games console actually is, what sort of functionality the demonpore 64 has and how it can bring together academics, game developers, gamers, and citizen scientists in order to solve the world’s biggest challenges. Kent talks through future games which will be available for the demonpore 64, including Poop of the Gods, 2021: A SARS Odyssey, Genomic Ranger, and Molecules of Mars. These games allow people to explore the molecular mysteries of poop, viral detection, chromosome structure, and martian soil! We then move on to talk about Kent’s life, from student, to academic, to entrepreneur. Kent talks fondly of his early days working on Drosophila genetics, and later at Halcyon Molecular a startup which was focussed around sequencing DNA with electron microscopy. He talks about how these experiences shaped his worldview around having a much greater impact by working on and caring about scientific tools rather than the science itself, and bringing these tools to the scientists with research questions. To learn more about the demonpore 64, check out Kent’s WeFunder campaign and also check out their website The nanopore cartridge shown at ~51:00 can be seen here: more information at the episode page here:
Lee Organick
27-05-2021
Lee Organick
Today we are joined by Lee Organick, a PhD student in the Molecular Information Systems Lab (MISL) at the University of Washington. Lee is a biologist turned computer scientist and engineer, quite a unique transition! She explains how she was “forced” to take a computer science class in her undergrad, which opened up a completely new field of interests. After this, she started incorporating more programming into her research, and as such slowly moved into more computational fields. This is how she eventually found herself at MISL, and has been programming molecules ever since. She talks about how the transition from biology to computer science was a difficult one, and how she suspects that she invested more time than the average student moving in the opposite direction. We then move on to talk about her main research area, DNA storage. Because we focussed on the specifics of DNA storage in our previous episode with Yuan-Jyue Chen (another member of MISL), we spoke more about the future of DNA storage, specifically where it fits in to the current data storage ecosystem. Lee argues that DNA is currently best suited archival and long term data storage, with many advantages over the traditionally used tape. Lee also talks us through a new project she is working on which involves augmenting the previously discussed DNA based image similarity search with Cas9! Finally we move onto an extremely interesting topic; that of the security concerns surrounding DNA data storage. We learn about how current sequencing machines may be vulnerable to buffer overflow attacks through the submission of malicious sequences, how sequencing leak can result in a nefarious third party being able to “spy” on other people’s pooled sequences, and some of our committee members even suggest some new potential exploits! ---Find more information at the episode page here:
William Poole
31-07-2021
William Poole
This week we spoke with William Poole, a graduate student at Caltech working on quite a few topics! His research spans synthetic/systems biology to molecular programming, software development to chemical reaction network (CRN) theory, machine learning to cell free systems. We certainly had a lot to talk about! We started off by discussing BioCRNPyler, a library which Will has been working on that allows for the rapid development and compilation of complex CRNs. He describes how BioCRNPyler can help you rapidly design CRNs in a variety of cellular contexts. The CRNs can then be simulated using any simulator/solver. We also discuss other software projects he is involved with such as Bioscrape and Vivarium. Next we move onto William’s research into chemical Boltzmann machines, what they are and how they are related to machine learning, while talking about how low molecular copy number systems might be able to perform more complex computation than high copy number systems. We also talk about how William got into molecular programming from his undergraduate degree, which focussed on physics and biology. He describes how his undergraduate research led him in various directions, and even into working in bioinformatics at the Institute of Systems Biology for a few years before pursuing graduate school. This ultimately spurred on a somewhat grand discussion on William’s “dream” for molecular programming. He is very concerned about climate change, and talks at length about how in the long term we might be able to program many of the materials around us to sequester carbon, and eventually “re-terraform” the earth. Finally, we asked why physicists and engineers are able to come together to build large scale projects such as the LHC and ISS, while no such projects exist for the biological sciences, and we speculate on what such a project could look like for our field... BioCRNPyler: more information at the episode page here:
Damien Woods
07-11-2021
Damien Woods
Today we’re talking with Damien Woods, a professor and molecular programmer at the Hamilton Institute, Maynooth University, Ireland. We first began by talking about how his early interests in dynamics and optical computers (the subject of his PhD thesis) led him to the field of molecular programming. We then move on to talking about one of Damien’s well known papers, Diverse and robust molecular algorithms using reprogrammable DNA self-assembly. In this paper, Damien describes the implementation of 21 algorithms using a 6-bit boolean circuit built out of a DNA tile-set. Damien and his team built a set of DNA tiles which could implement any algorithm allowable by that 6-bit computer (the tiles are 6-bit universal). Damien describes how this allows anyone to wake up in the morning, design an algorithm, retrieve the appropriate tiles from the fridge, mix them and begin running the algorithm in a test tube on the very same day. This clearly has its advantages over other systems, which may require someone to wait for the DNA synthesis of their system before an implementation can be made. The readout of these circuits is by AFM to see a tape-recording of the computation, and so this paper generated a lot of pretty pictures! We then moved on to talk about potential implementations of more complex computers, how Damien et al.’s 6-bit boolean circuit might be scaled up, and how the number of required tiles scales with the computational complexity (it’s linear!). This led us on to an extended discussion about universal tile-sets, their existence, and their ability to be implemented in DNA. Finally we moved on to Damien’s experience in academia. He’s been to quite a few places, and has worked on many different things. He explains how his experience running a lab in two different countries differed, and how this shaped the way he runs his research group. Diverse and robust molecular algorithms using reprogrammable DNA self-assembly paper: more information at the episode page here:
Sam Schaffter
18-02-2022
Sam Schaffter
Join us for a chat with Sam Schaffter, a postdoc at NIST working on realizing complex transcription-based strand displacement in living systems. We start the conversation with the story of how he made the transition from the molecular biology of food to molecular programming. We then move on to the details of his research on transcriptional circuits including where the idea came from and the trials of taking molecular computing from the test tube to cell systems. He tells us about the differences and similarities between academic and government research and how everything is a “measurement” when you work for NIST. We round out the conversation with Sam’s dreams of the future of nucleic acid-based sensors for diagnostic and control purposes and the research he would like to see in the next 5, 10, 25 and 50 years to advance the field toward application. Sam conducted his PhD research in the field of DNA nanotechnology and DNA computing, working in Rebecca Schulman’s group at Johns Hopkins. He developed synthetic transcription-based networks with dynamics programmed via Franklin-Watson-Crick base pairing rules. These in vitro networks emulated key functionalities of cellular genetic regulatory networks and thus could serve as a programmable “synthetic genome” for controlling nucleic acid materials and devices, such as DNA nanostructures and DNA-responsive hydrogels. The goal of his research was to engineer synthetic materials capable of sophisticated behaviors seen in biology including hierarchical differentiation or self-healing. For this work, he won the 2021 Robert Dirks prize for molecular programming As a National Research Council (NRC) postdoctoral fellow at NIST, Sam is interested in moving DNA computing circuits from the test tube to living cells. Current DNA-based circuits are only single use and suffer from degradation in vivo, limiting their practical applications. To overcome these limitations, Sam’s current research focuses on transcriptionally encoding RNA-based circuits, equivalent to those developed in DNA computing, that can operate continuously inside living cells. These circuits could be programmed to recognize complex differential gene expression patterns in real-time in vivo, potentially enabling a new class of living measurement systems. Sam’s project at NIST: RNA strand displacement circuits: for applications to the NIST Cellular Engineering Group: non-US citizens, the process for applying is essentially to contact someone at NIST you want to work with and to discuss potential projects. If NIST has available funding to hire students for a specific project, then the student can be hired through an external university. This process is actually done for both US an non-US citizens depending on need / the situation. There isn’t a funding mechanism like the NRC fellowship for non-US citizens so it depends more heavily on existing funding. But nonetheless, any interested international students are encouraged to reach out about available opportunities. ---Find more information at the episode page here: