Episode Summary: Millions of people die every year from chronic diseases. Traditional drug discovery has failed in identifying solutions to many of these persistent health challenges. Functional genomics is offering a way forward by identifying gene networks and enabling the development of drugs with very specific targets. But, rather than just relying on gene targets within humans, Linda and her company, Fauna Bio, are casting a wider net across the animal kingdom. Extreme adaptation is common ...
Jun 01, 2023•50 min•Season 5Ep. 2
Episode Summary The expression of genes in our genome to produce proteins and non-coding RNAs, the building blocks of life, is critical to enable life and human biology. So, the ability to predict how much of a gene is expressed based on that gene’s regulatory DNA, or promoter sequence, would help us both understand gene expression, regulation, and evolution, and would also help us design new, synthetic genes for better cell therapies, gene therapies, and other genomic medicines in bioengineerin...
Mar 09, 2023•55 min•Season 5Ep. 1
Episode Summary: In this very special episode of Translation, Seth is joined by Ash Trotman-Grant to demystify spinning out from academia. Much of this knowledge has so far only been available to select groups of academics and PhD founders are at a disadvantage – some potentially breakthrough technologies never saw the light of day and didn’t get a chance to have a real impact. We want to bring the power of the tech transfer process back to entrepreneurial scientists. Enter the Spinout Playbook ...
Dec 29, 2022•42 min•Season 4Ep. 7
Episode Summary Chimeric antigen receptors, or CARs, repurpose the build-in targeting and homing signals of our immune system to direct T cells to find and eliminate cancers. Although CAR-T cells have transformed the care of liquid tumors in the circulating blood, like B cell leukemia and lymphoma, CAR-T therapy has shown limited efficacy against solid tumors. To unlock the full potential of CAR-T therapies, better receptor designs are needed. Unfortunately, the space of potential designs is too...
Nov 09, 2022•1 hr 38 min•Season 4Ep. 6
Episode Summary: DNA is an ideal molecule for storing information in our genomes because it’s stable, programmable, and well understood. The same qualities make DNA a great building block or construction material for nanoscale biomolecular structures that have nothing to do with our genome, like molecular scaffolds created by folding DNA into 2D and 3D shapes. This technology is known as DNA origami. However, the practical applications of DNA origami are limited by spontaneous growth and poor re...
Nov 03, 2022•39 min•Season 4Ep. 5
Episode Summary: Technologies like next-generation sequencing allow us to understand which RNA transcripts and proteins are expressed in biological tissues. However, it’s often equally important to understand how cells or molecules are positioned relative to one another! Whether it be a cell changing its shape, an organelle ramping up a metabolic process, or a DNA molecule traveling across the nucleus, understanding spatial context is critical. Current approaches for spatial sequencing are limit...
Oct 10, 2022•29 min•Season 4Ep. 4
Episode Summary: Antibodies are one of the greatest tools we have in our therapeutic arsenal and have transformed the way we treat cancer and autoimmunity. But we still largely develop these drugs using guess and check methods, massively slowing down the process. However, our own B cells are constantly making new antibodies against the pathogens and diseases we routinely suffer from, creating a gold mine of drugs floating around inside all of us. We just need to find them! Recognizing this chall...
Jun 08, 2022•54 min•Season 4Ep. 3
Episode Summary Imagine if every graphics design company built its own version of Photoshop in-house. That’s exactly what’s happening today in biology research. Ten-fold increases in data every two years are forcing every biology team to build out their own, in-house bioinformatics stack to store, clean, pipe, and manage the massive volumes of data generated by their experiments. All that work has to happen even before teams can analyze the results! Recognizing this obstacle to high-throughput b...
Jun 02, 2022•1 hr•Season 4Ep. 2
Episode Summary: Evolution is happening even at the cellular scale. Whether it's a virus, a bacterial pathogen, or a cancer cell, disease-causing agents are responding to the therapies we throw at them, updating their genes and molecular pathways to resist death. As a trained microbiologist, Nick Goldner and his co-founder Chris Bulow spent their years in grad school using -omics data to overcome antibiotic resistance in bacteria which led to their first company Viosera. As they struggled with t...
Jan 27, 2022•1 hr 4 min•Season 4Ep. 1
Episode Summary: When COVID-19 hit and society decided to use mRNA vaccines for the first time, many questions remained about whether RNA itself was ready for the challenge. But three scientists at Stanford University who had barely worked with each other before the pandemic realized that RNA’s limitations were merely a design challenge and not an issue with the substrate itself. Through emails and zooms, Kathrin, Gun, and Hannah built a tool to massively test RNA designs. With it, they screened...
Oct 14, 2021•49 min•Season 3Ep. 6
Episode Summary: COVID-19 tests have become synonymous with jamming a swab up our nose to find out whether we have an active infection. But as we progress through this pandemic, a test that tells us whether people have antibodies against the virus will be massively important to creating public health initiatives and deciding who to vaccinate next. Unfortunately, these serology tests are exceedingly tedious to perform, inhibiting their widespread use. Realizing this problem, Susanna talks us thro...
Oct 07, 2021•37 min•Season 3Ep. 5
Episode Summary: Brain machine interfaces untangle the complex web of neurons firing in our brains and relay the underlying meaning to a computer. These devices are being adapted to help patients regain motor control, monitor our mental well being, and may one day even make us more empathetic. State of the art methods to do this have massive trade-offs, either being high resolution yet requiring devices to be embedded in our heads or low resolution but non-invasive. Finding a key middle ground, ...
Sep 30, 2021•58 min•Season 3Ep. 4
Episode Summary: Enzymes that break down other proteins, or proteases, could be used as a powerful therapeutic if they could specifically chew-up disease causing entities. However many proteases are non-specific, breaking any protein in their path, while the specific ones target proteins that would provide no therapeutic benefit. Travis and his colleagues developed a riff on the method known as PANCE that utilizes bacteria and bacterial viruses known as phages to evolve proteins toward a specifi...
Sep 23, 2021•41 min•Season 3Ep. 3
Episode Summary: Novel drugs that boost the immune system to fight cancer have become pharma darlings in the few short years since their approval. These drugs, known as immunotherapies, have so far focused on improving T cell responses and can be used to cure a multitude of different cancer types. Yet more often than not, immunotherapies have no effect on a patient, leaving doctors guessing on whether to prescribe the drug. To find the reason why some people respond while others don’t, Kevin and...
Sep 16, 2021•49 min•Season 3Ep. 2
Episode Summary: In a single decade, CRISPR has made a dramatic impact on literally every facet of biotechnology. This game-changing system is traditionally programmed to make cuts at very specific parts of the genome, altering the code to cure disease. But a new class of CRISPRs discovered by Leo’s colleagues don’t simply cut DNA -- they integrate entirely new genetic material at targeted locations. With it, Leo generates a new method to perform very specific and highly efficient genome enginee...
Sep 09, 2021•58 min•Season 3Ep. 1
Whether it's Multiple Sclerosis, Type 1 Diabetes, Lupus, or Crohn's Disease, autoimmunity is a rapidly growing problem that traditional pharmaceuticals have failed to completely cure. While these diseases have very different symptoms, they all have the same root cause -- the body’s immune system is attacking its own healthy organs. Lurking within ourselves are a group of T cells called regulatory T cells that have the power to suppress immune function. These cells have huge potential to be engin...
Feb 25, 2021•41 min•Season 2Ep. 5
Engineered T cells that hunt and kill blood cancers have recently obtained three landmark FDA approvals, forever changing the way we treat this disease. Even with its massive clinical success, these cells come with life-threatening neurotoxicities. But is neurotoxicity a set feature of using T cell therapies or is our engineering accidentally targeting the brain? Utilizing advances in bioinformatics and the huge sequencing datasets available to science, Kevin uncovers similarities between a cell...
Feb 18, 2021•38 min•Season 2Ep. 4
Small molecules are a pillar of human health, making up a majority of the drugs we have in our healthcare arsenal. Many of these drugs are obtained by utilizing synthetic chemistry to modify the composition of some small molecule found in nature. Derivatives of tropane alkaloids, for example, alleviate neuromuscular disorders and are derived from a chemical found in nightshade plants. However, sourcing these plants have become exceedingly difficult as climate change, the pandemic, and geopolitic...
Feb 11, 2021•53 min•Season 2Ep. 3
Bacteria are rapidly evolving ways to resist antibiotics, causing minor infections to become life-threatening events. Compounding the problem, new antibiotics have been incredibly challenging to develop and pharma is economically disincentivized to invest in finding them. James Martin and his colleagues Joseph Sheehan and Benjamin Bratton took on this challenge, developing an extremely potent antibiotic that targets multiple different classes of bacteria. James tells the story of identifying thi...
Feb 04, 2021•37 min•Season 2Ep. 2
Hundreds of iterations of immune cells that are engineered to kill cancer have already been designed. Corina reached outside of this box to use the same synthetic biology principles to engineer T cells to attack senescent cells, a cell type that contributes to diseases of aging. Corina walks us through how her engineered T cells know the difference between a diseased cell and healthy tissue, how she stumbled upon the chimeric antigen receptor that made this possible, and how these new T cells ar...
Jan 28, 2021•26 min•Season 2Ep. 1
Could all the leading COVID19 vaccines have a fatal flaw in their design? A dizzying number of vaccines are being developed to protect society from the dangers of COVID19, each with its own benefits and pitfalls. At HelixNano, Nikolai Eroshenko and his team are designing a special type of vaccine with increased attention to ensuring that this protective medicine doesn't accidentally improve the virus's ability to infect cells or drive the immune system to cause collateral damage. Nikolai describ...
Nov 03, 2020•39 min•Season 1Ep. 4
Powered by synthetic biology, Pierce Ogden makes ALL possible mutations to an adeno-associated virus (AAV) outer shell and rapidly screens them to dissect their attributes. Pierce discusses the technological advances that make this breakthrough screen possible and the novel properties that were discovered. AAVs are rapidly becoming the prefered way to perform gene therapy, correcting cells that carry disease-causing mutations through genetic modification. This technology forms the basis for comp...
Oct 27, 2020•51 min•Season 1Ep. 3
Commodity molecules are vital ingredients for everything important to our modern world including food, energy, and medicine. However, creating these molecules still largely relies on old processes that suffer from low yield, laborious methods, and unsustainable inputs and byproducts. Tina envisions a world where all molecules are created quickly, easily, and sustainably through enzymes, biology’s chemical catalyst. Here, Tina describes how she used an extremely powerful method called directed ev...
Oct 20, 2020•44 min•Season 1Ep. 2
Protein engineering has been dominated by two opposing paradigms; directed evolution, a massive screening technique, and rational design, a completely computational approach. Surge has fused these two paradigms by developing a machine learning technique that discovers an optimal protein design by training on a low number of engineered proteins. Here, Surge discusses how this hybrid method works, how it enabled the creation of better fluorophores and enzymes, and what this method will unlock next...
Oct 06, 2020•30 min•Season 1Ep. 1
