Season 3, Episode 5: Illuminating Immunity to COVID-19 with Susanna Elledge

First Author: Susanna Elledge

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, Susana talks us through how she utilized protein engineering to create a novel serology test that is massively easier and quicker than traditional methods. Importantly, this test can be used in resource low settings to help end the pandemic worldwide.

About the Author

• Susanna’s scientist parents and love for the natural world drove her to research biology and chemistry.

• Susanna is most excited about adding new dimensions to biomolecules through bioconjugation to enhance their function.

Key Takeaways

• A serology test is used to see whether a person has antibodies against a specific pathogen.

• Positive serology tests can tell us whether getting the disease led to immunity, whether a vaccine worked, or whether a person is protected from new variants.

• This could be massively useful to help understand who is protected and who to vaccinate next to finally beat the SARS-CoV-2 pandemic.

• Traditional serology tests use hard to scale and overly laborious methods that hinder their adoption, especially in a low resource setting.

• Susanna used protein engineering and leveraged the shape of antibodies to develop an entirely new serology test.

• She engineered protein fusions that when simply mixed with a human sample such as serum or saliva, will generate light if antibodies against COVID-19 are present.

• This much easier test as well as the variety of human samples it can use as inputs make it a much more approachable option and enables its use in low-resource settings.

Translation

• Susanna and her colleagues are working to make this test available for field studies by making the protein easier to ship and making a handheld device that can measure the readout.

• Productizing this test will require more research in how to stabilize the components, incorporate controls, and most importantly, make it high-throughput.

• Susanna hopes to leverage this technology to help us beat the variants of SARS-CoV-2 and eventually rapidly test for other infectious diseases and autoimmunity.

Paper: Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection

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Season 3, Episode 4: Listening to Neurons with Sumner Norman

First Author: Sumner Norman

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, Sumner uses advances in ultrasound to monitor the brain activity of monkeys performing specific tasks. With this data, he can not only record the brain activity associated with performing the task itself but also the intention of doing it before the subject even has a chance to move.

About the Author

• Sumner started his career in mechanical and aerospace engineering, performing research on haptics and mechatronics.

• This developed in him the love for how humans and computers interact, leading him to earn a PhD developing exoskeleton robots for motor learning and control.

• Through this, he realized that to translate these technologies, we need better methods to get information out of the brain.

Key Takeaways

• Ultrasound technologies are leveraged to monitor brain activity.

• The signal that is generated when these methods “listen” to the brain is extremely complex and entangled, akin to trying to make out a sentence from across a loud stadium.

• Sumner taught monkeys how to perform a task, reading the brain with ultrasound and using machine learning to decode the message.

• With it, they were able to read which way the monkey intended to move, when the movement would occur, which way the monkey actually moved, and whether it would move its hands or eyes.

Translation

• This technology has massive potential to help those suffering from motor impairment and could one day connect us all on a deeper level.

• To get there, the device will need to be optimized to find the best way to maximize signal-to-noise but minimize invasiveness.

• Additionally, advances in miniaturization, wireless connections, lowered cost of goods, and finding the right balance between AI and BMI control are needed to get this extremely new technology into the hands of everyone.

Paper: Single-trial decoding of movement intentions using functional ultrasound neuroimaging

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Season 3, Episode 3: Phage Evolved Medicine with Travis Blum

First Author: Travis Blum

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 specific goal. With it, he retrains the sequence-specific protease, botulinum neurotoxin, toward new targets and away from its original ones. The novel enzymes Travis generates have the potential to not only stimulate nerve regeneration but also deliver itself to the correct cell types for a whole new type of therapy. 

About the Author

• Travis is a postdoc who performed this work in the lab of Professor David Liu at Harvard University. The Liu lab is famous for engineering and evolving proteins that can be utilized as massively impactful tools for overcoming diverse diseases.  

• Travis’s teachers fostered a curiosity that created a passion for chemistry and ultimately led him to engineer new biochemistries. 

Key Takeaways

• Proteases are enzymes that cut up other proteins.

• Proteases can either be non-specific, a nuke obliterating any protein in their path,  or sequence-specific, a heat-seeking missile only cutting very specific protein motifs.

• Sequence-specific proteases that target disease-causing proteins would make great drugs but therapeutically useful proteases rarely exist in nature.

• Travis focuses on re-engineering the sequence-specific protease known as botulinum neurotoxin so that it cuts an entirely new, therapeutically relevant protein sequence.

• Using a method called PANCE that utilizes bacteria and bacterial viruses (phages), Travis trains botulinum neurotoxin toward cutting a new target and leaving its original target alone.

Translation

• Botulinum neurotoxin has a cutting domain that Travis engineered toward a therapeutically relevant target, and a targeting domain that delivers the protein toward neurons.

• The enzymes generated could be used to cure neural pathologies but the PANCE could also be applied to change which cell type the protease targets, creating a highly programmable therapeutic protease platform.

• The platform has a ton of interest from industry and Travis is continuing to work on it outside of academia so that these proteases make it to the clinic and impact patient lives.

Paper: Phage-assisted evolution of botulinum neurotoxin proteases with reprogrammed specificity

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