Translation - Illuminating Immunity to COVID-19 with Susanna Elledge

Illuminating Immunity to COVID-19 with Susanna Elledge

10/07/21 • 36 min

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 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.

Episode Notes:

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.

First Author: Susanna Elledge

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

Episode Summary:

Episode Notes:

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.

First Author: Susanna Elledge

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

Previous Episode

Listening to Neurons with 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.

Episode Notes:

About the Author

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

First Author: Sumner Norman

Paper:

Single-trial decoding of movement intentions using functional ultrasound neuroimaging

Next Episode

Screening for Enhanced RNA Vaccines with Kathrin Leppek, Gun Woo Byeon, and Hannah Wayment-Steele

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 for RNA with better functionality, increasing the stability and expression of the protein they encode and ultimately creating a platform to improve these life-saving vaccines.

Episode Notes:

About the Authors

Hannah, Gun, and Kathrin had all been separately researching various aspects of genetics and RNA before the pandemic.
When COVID hit and RNA vaccines were being built, the three realized they had newly complementary skill sets.
They set aside their individual projects, leveraged their unique backgrounds, and worked in shifts to abide by social distance rules in order to solve multiple issues facing RNA as a substrate for vaccines.

Key Takeaways

RNA holds great potential for therapies and vaccines as they are highly programmable, extremely flexible, and are much easier to scale than other options.
But RNA is hard to deploy for vaccines because it is extremely unstable both in the body and on the shelf.
Enhancing the expression and stability of RNA allows us to reduce the amount needed to give a person, increasing the number of people that can be vaccinated.
The three designed PERSIST-seq to test a multitude of RNA designs in one-pot by leveraging synthetic biology and next generation sequencing.
They also leveraged citizen science through a “game” called Eterna in order to optimize sequences using the collective brain power of humanity.
With it in they found synonymous mutations and alterations to the untranslated regions that changed RNA folding and improved stability and translation.

Translation

PERSIST-seq must still be validated in animal models to fully connect how improvements on stability and expression alter vaccine efficacy.
The team is ready to leverage their approach through licensing to help RNA vaccine companies improve their designs.
The design rules and method to discover them can be used to enhance any RNA therapeutic that will undoubtedly be coming through the pipeline soon.

First Authors: Kathrin Leppek, Gun Woo Byeon, and Hannah Wayment-Steele

Paper: Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics