The molpigs Podcast

In this episode the molpigs team talks with Greg Tikhomirov about his experience starting a new molecular programming lab and his visions for “a new nanotechnology”. We learn about his journey from wanting to build large, beautiful molecules to his work at the interface between molecular design and material science.

Greg Tikhomirov is an assistant professor in Electrical Engineering and Computer Sciences, with a background in chemistry, bioengineering, medicine, and nanotechnology. He has a longstanding dream to engineer life-like artificial systems, motivated by the realization that incomprehensible natural complexity arises from comprehensible fundamental laws. Ti Lab at Berkeley is pursuing the design and fabrication of devices with atomic precision by combining the strengths of rational top-down engineering and bottom-up biomolecular assembly. A key goal is to adopt the powerful but still proof-of-concept self-assembly approaches of DNA nanotechnology to engineer new, useful devices.

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Find more information at the episode page here:
https://podcast.molpi.gs/media/tikhomirov-g-cb5ef2637de05b5b/

Join the molpigs team for a conversation with Eva Bertosin about her work on building nanoscale rotors during her PhD with Hendrik Dietz. This is a "poster podcast," so we will occasionally be referencing figures in the associated poster which can be found at the link below. The DNA origami rotor was inspired by the rotational mechanism of ATP synthase, which Eva and her colleagues had to simplify and abstract to create a functional DNA structure which could demonstrate rotational diffusion. She explains how they used cryoEM to optimize design, and how new tools for analyzing cryo data made the ambitious data analysis involved in this process possible. And the promises of using molecular simulation to help inform design. We round out the conversation with discussion of how she got into DNA design, visions for the future, and advice to future students about tackling huge projects.

Eva is a postdoc in the Cees Dekker's research group at the Technical University of Delft. Her work is focussed on building artificial systems that are inspired by natural components of the cell. In particular, she is working on biomimetic systems to study transport of molecules through the nuclear pore complex. She obtained her PhD in 2021 working in Hendrik Dietz' group at the Technical University of Munich. During this time, she built a novel rotating nanostructure made of DNA origami components with interlocked and coupled motion. This work was chosen as one of the finalists of the CeNS Nano Innovation Award 2021. She got her MSc degree at the Technical University of Munich and her BSc in physics studying at Padua University and at the Georg-August-University Göttingen.

Poster: https://podcast.molpi.gs/media/bertosin-e-db84e966a4c6b894/poster.pdf
Video: https://podcast.molpi.gs/media/bertosin-e-db84e966a4c6b894/brownian.mp4

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Find more information at the episode page here:
https://podcast.molpi.gs/media/bertosin-e-db84e966a4c6b894/

Join the molpigs team as they have a discussion with one of the theoretical giants of molecular programming: Anne Condon. Over the wide-ranging conversation, she shares her insights on NP-complete problems, solving RNA folding with good data, and how best to teach and mentor students in a manner that creates great researchers and facilitates diversity in the field.

Anne Condon is a professor of Computer Science at the University of British Columbia, of which she was formerly head of department, and also a fellow of the Royal Society of Canada. She is known for her extensive work in computational complexity theory and design of algorithms, in the context of bioinformatics, hardware verification, combinatorial auctions, and of course, DNA computing. As well as numerous awards for her work in Computer Science from bodies including the ACM, she has also received many awards for her leadership in advancing women in computing, and has previously held the NSERC/General Motors Canada Chair for Women in Science. She completed her bachelor’s degree at University College Cork, and her doctorate at the University of Washington.

For listeners who would like to skip to the less technical parts of the interview, and hear Anne’s insights on diversity, mentorship and creating a positive experience for students, that section begins 28:33 into the episode.

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Find more information at the episode page here:
https://podcast.molpi.gs/media/condon-a-331aad943a3b7c48/

On this episode Hannah, Boya, Erik and new co-host Dhaval sit down with Jurek Kozyra, founder of the molecular programming startup, Nanovery. Over the course of this wide-ranging interview, he tells us about how learning biology can help your dating life, his PhD work at the intersection of biotech and computer science and his early ventures in cherry picking and private investigation before diving into his story of building a successful startup with funders, employees, and lab space.

Jurek Kozyra is the founder and CEO of Nanovery. He obtained his BSc in Computer Science with Artificial Intelligence from the University of Nottingham, where he studied bio-inspired and unconventional computing. Afterwards, Jurek earned his PhD in DNA nanotechnology and DNA computing from Newcastle University working at ICOS (one of the leading computational synthetic biology research groups in the UK). He was also an entrepreneurial lead for a university biotech spin-out based on the DNA barcoding technology he developed. In 2018 Jurek started Nanovery—a molecular diagnostic company developing DNA nanorobots for early detection of diseases from blood samples. The mission of the company is to enable accurate and simple testing closer to the patient bedside.

Nanovery: https://www.nanovery.co.uk

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Find more information at the episode page here:
https://podcast.molpi.gs/media/kozyra-j-7f09821bb076e517/

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: https://www.nist.gov/programs-projects/cellular-measurement-and-computation-rna-circuits
Co-transcriptional RNA strand displacement circuits: https://www.biorxiv.org/content/10.1101/2021.07.20.450530v1
Call for applications to the NIST Cellular Engineering Group: https://molpi.gs/files/220114-nist-call.pdf

For 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.

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Find more information at the episode page here:
https://podcast.molpi.gs/media/schaffter-s-1c8799780ad4af6f/

Join us for a relaxed chat with Sifang Chen, a science policy post-doc, for a slightly different discussion. We speak about Sifang’s past, how she got into DNA nanotech and molecular programming, her research on biosensors and DNA programmable materials, and how she switched to this field from quantum and graphene based devices. We then moved on to talking about science in a broader scope, starting off with the big question of how Synthetic Biology and related fields will help in the fight against climate change, and the problems we face, both from a policy and science perspective. Moving into policy is certainly unconventional, and Sifang explains the transition, and the skills required to do so, before diving into the specifics of what her job entails, how she communicates with lawmakers, and the difficulties she faces in this line of work.

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Find more information at the episode page here:
https://podcast.molpi.gs/media/chen-s-f9bc60e3bc0abb74/

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: https://www.nature.com/articles/s41586-019-1014-9

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Find more information at the episode page here:
https://podcast.molpi.gs/media/woods-d-2ba60fd172cf0f39/

In our latest Meet The Molecular Programmer, our guest was David Doty. We dove right in to the way he splits his research time, which has been between software development, theory, and sometimes experiments! He talks about how his experience doing his first experiment made him realise the need for good software, as good software enables good experiments.

We then moved on to discussing what “nice” theory is. Doty explains how typically people seek to publish the most elegant, and often complicated theory in conferences and journals, but that this rarely translates to experimentation which can be done in the lab. When asked for an example of a time that he saw elegant theory married to beautiful experiment, he gave our own host’s (Anastasia) most recent paper on crisscross assembly!

Finally we moved on to more personal aspects of Doty’s academic life, talking about how he moved into the field, his experience switching topics twice during his PhD, and his rather unique marriage proposal! You’ll have to give the podcast a listen to find out how exactly he did it...

Crisscross paper: https://www.nature.com/articles/s41467-021-21755-7
Dave's wedding slides: https://web.cs.ucdavis.edu/~doty/papers/wedding-presentation.pdf

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Find more information at the episode page here:
https://podcast.molpi.gs/media/doty-d-dd5c60f6a9ff59ca/

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: https://github.com/BuildACell/BioCRNPyler
Bioscrape: https://github.com/biocircuits/bioscrape
Vivarium: https://github.com/vivarium-collective/vivarium-core

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Find more information at the episode page here:
https://podcast.molpi.gs/media/poole-w-9a5d873910edd591/

Join us in this experimental episode as our conversation turns inwards! Instead of finding out about the life and interests of someone from the field, we share some of our own views and anecdotes. We discuss a little about who we are, graduate school, the definition of the field, and more.

Hannah, the founder of molpigs, gives a bit of an insight into what the motivation for starting molpigs was and what they hope this project will achieve. Boya, our newsletter editor, explains how learning more about psychology is helping her to be a more effective researcher. Anastasia, who shares podcast editing duties with Hannah, gives some perspectives on how fundamental DNA is to the field of molecular programming. Georgeos, who manages our social media and money, tells us why he'd much rather be a scientist today than the 19th century.

We also give an update on the status of our sister project, the Molecular Programming Society, which is currently writing the ‘Art of Molecular Programming’ textbook. The project is rapidly growing to include dozens and dozens of members of our field. If you want to keep up-to-date with their progress, follow them on Twitter @MolProgSoc and subscribe to their newsletter.

Anastasia: https://www.linkedin.com/in/anastasiaershova/
Boya: https://boyawang.weebly.com
Georgeos: https://gh464.user.srcf.net/
Hannah: https://ha.nnah.io/
MPS Twitter: https://twitter.com/MolProgSoc
MPS Newsletter: https://lists.molecularprogrammers.org

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Find more information at the episode page here:
https://podcast.molpi.gs/media/panel1-a89e43c06e4d75be/