UNews - Amy Henrickson

U of L master’s student helps develop a better way to measure drug loading, enhance vaccine efficacy

caroline.zentner — Wed, 07 Apr 2021 19:53:44 +0000

In a recently published article in ACS Nano, a high-impact nanoscience and nanotechnology journal, ��Ѹ��Դ��߿�Ƭ of Lethbridge master’s student Amy Henrickson (BSc ’17) and her collaborators at the ��Ѹ��Դ��߿�Ƭ of British Columbia have devised a better way of measuring drug loading in lipid nanoparticle formulations (LNPs) using analytical ultracentrifugation (AUC).

These formulations are typically used in gene therapies and, more recently, in the development of some COVID vaccines. Lipid nanoparticles are very small and can be thought of as a capsule for delivering a treatment. Lipids occur naturally in the body in the form of fats, hormones and certain vitamins. In the case of the COVID vaccines, lipid nanoparticles are loaded with RNA that instructs the human body to recognize the spike proteins on the SARS-CoV-2 virus and thus build immunity.

For the quality control of these formulations, researchers need an accurate way of determining the RNA loading state of LNP formulations, because only a narrow range of RNA loading leads to the desired biological effect and assures patient safety; empty or overloaded LNPs are ineffective and can increase the potential for allergic reactions.

“The new method we developed is able to tell us the ratio of RNA to lipid,” says Henrickson, who studies under biophysicist Dr. Borries Demeler, a Canada 150 Research Chair. “There are advantages and disadvantages to all techniques, but many other methods involve low resolution bulk observations that lack the necessary detail. This method is able to tell if any LNPs are empty and if everything’s properly loaded with the preparation.”

The method, developed over the past two years at the Canadian Center for Hydrodynamics at the U of L, uses multi-wavelength AUC to measure the spectral profile of nanoparticle preparations, quantifying the RNA contained in the LNP. They also use heavy water to measure densities of preparations, which is sensitive to the RNA load. The work was done in collaboration with Pieter Cullis’ group at UBC, where they are working on developing lipid nanoparticles for gene therapy.

“In her short time as a graduate student in the Department of Chemistry & Biochemistry, Amy has already amassed 10 publications, including first-author contributions like the ACS Nano publication,” says Demeler. “Amy is a star student who has helped our group make significant and high-impact progress in many important fields, contributing novel discoveries to gene therapy and vaccine development.”

The Canadian Center for Hydrodynamics has also received a grant from the Biomolecular Interaction Technologies Center organization, which is based in the United States. The grant is to develop viral vector characterization in adeno-associated viruses (AAVs) using AUC, which forms the basis of Henrickson’s PhD work.

AAVs, which are not known to cause disease, are small viruses that can be used for gene delivery in the treatment of a variety of human diseases. Preparations made with AAVs tend to exhibit a mixture of loaded and unloaded viral capsids (the protein shell of a virus).

“Many methods currently in use can’t differentiate between different components in a preparation,” says Henrickson. “I’m trying to use AUC to create two or three different methods that will all be able to characterize an AAV formulation and tell you if there’s any free DNA, empty AAVs, loaded or partially loaded AAVs, or aggregates in the preparation.”

Early research opportunities lead to publications for U of L students

caroline.zentner — Mon, 11 Jan 2021 21:43:16 +0000

Two ��Ѹ��Դ��߿�Ƭ of Lethbridge students can add publications to their resumés after they took advantage of getting involved in research early in their university education. Not only have they published papers in major journals, they’ve also collaborated with other departments within the U of L and internationally.

From left to right are Dr. Borries Demeler, Amy Henrickson and Marielle Stoutjesdyk.

Marielle Stoutjesdyk, an undergraduate student in the Department of Physics, and Amy Henrickson (BSc ’17), a master’s student in the Department of Chemistry & Biochemistry, work in Dr. Borries Demeler’s lab. Demeler is a Canada 150 Research Chair for Biophysics and director of the Canadian Center for Hydrodynamics, which uses analytical ultracentrifugation to analyze molecules in solution.

Stoutjesdyk has been the first author on two scientific papers published in an international journal, all while working on her undergraduate degree. Her first project involved testing out a new, highly technical analytical ultracentrifuge, specifically measuring how much its titanium rotor stretched when spinning at 60,000 revolutions per minute.

“Imagine being on a merry-go-round and spinning so fast you feel gravity pushing you 300,000 times stronger than usual,” says Stoutjesdyk. “The 12-pound titanium rotor in the ultracentrifuge experiences these forces and, as a result, it begins to stretch out. This causes errors in the analytical software that’s collecting data on the molecules being spun. My job was to correct this error so I designed a novel centerpiece that measures the stretching of the rotor and errors from the optical systems.”

Her paper was published in the European Biophysics Journal and earned her first place in a poster presentation in the 2019 Chinook Symposium for Chemistry and Biochemistry. She also presented her research at national conferences in Toronto and Montreal.

“I went on to study the compression capabilities of the ultracentrifuge,” she says. “We found liquids would experience some compression when we spun them as fast as we could. This demanded further inspection as the compressibility of liquids is an important parameter when investigating molecules in a solution.”

The paper that resulted from this work was recently published, also in the European Biophysics Journal, with Henrickson and colleagues from the ��Ѹ��Դ��߿�Ƭ of Montana as co-authors.

Henrickson has been involved in multi-wavelength analytical centrifugation, a new technique that provides improved resolution and is only available at the U of L. It’s used for studying solution interactions where the interacting molecules contain different spectral properties. Through a collaboration with Dr. Renwick Dobson at New Zealand’s ��Ѹ��Դ��߿�Ƭ of Canterbury, three graduate students came to the U of L to learn how to design, run and analyze data using analytical ultracentrifugation. Henrickson helped teach the students about multi-wavelength techniques.

“From these collaborations, we have had the opportunity to publish a paper in the European Biophysics Journal and we are in the process of undergoing reviews of a second paper,” says Henrickson. “Collaborations within science are of significant importance as they allow research groups to gain experience and expertise in fields they normally wouldn’t have access to.”

The accomplishments of these students demonstrate the opportunities for research that U of L students can access early on in their university careers.

“Marielle and Amy have already built impressive resumés as students and that will help them in their careers,” says Demeler. “Their achievements as students demonstrate their strengths as scientists and open up many opportunities for their future work.”

Partnership gives U of L student one-of-a-kind learning opportunity

caroline.zentner — Wed, 17 Jun 2020 19:29:57 +0000

A partnership between API (Applied Pharmaceutical Innovation) and the ��Ѹ��Դ��߿�Ƭ of Lethbridge led to a unique training opportunity for one graduate student.

Amy Henrickson (BSc ’17) started her master’s in January, working under the supervision of Dr. Borries Demeler, a professor in the Department of Chemistry & Biochemistry, in the Canadian Center for Hydrodynamics. She’s focusing her work on adeno-associated viruses (AAVs).

These small viruses, which are not known to cause disease in humans, elicit a mild immune response in the body and that makes them attractive for use in delivering gene therapies. In therapeutic applications, AAVs can be engineered to deliver DNA to target cells. Using AAVs in this manner is an area of growing interest and clinical trials have produced promising results in several diseases such as Parkinson’s disease, hemophilia and cystic fibrosis.

“I wanted to learn how to produce adeno-associated viruses and, since there’s nobody at the ��Ѹ��Դ��߿�Ƭ of Lethbridge who does that right now, I needed to go somewhere and find out how it’s done,” says Henrickson.

Demeler and Henrickson had already been in touch with Viviana Gradinaru, a professor of neuroscience and biological engineering at the California Institute of Technology (Caltech), and thanks to funding from API, Henrickson spent 10 days in February at Caltech’s CLOVER (Clarity Optogenetics & Vector Engineering) Center lab.

“I’m really appreciative of API for this great experience and for Viviana and her lab group to take me on and spend all the time they did training me,” says Henrickson. “They were all really nice and super willing to help — it was great. We did two preparations of adeno viruses while I was there. The person who was teaching me did one, mostly just to show me, and then the second prep, I did by myself with her watching. It was good to have somebody there to walk me through it.”

Once she is able to produce AAVs in the lab, Henrickson will concentrate on developing a new biophysical method using multi-wavelength analytical ultracentrifugation to accurately determine the amount of empty versus loaded viruses in a given preparation. During the production of AAVs, a portion of the viruses will encode without the desired preparation inside them. So far, scientists don’t have a good method to measure them in a preparation.

“In the medical field, empty viruses are considered contaminants,” says Henrickson. “If you were to inject it into a patient, the empty ones wouldn’t be delivering the desired treatment. All they would be doing is increasing the immune response. So, you want to limit the number of empty viruses in a preparation.”

Unfortunately, Henrickson hasn’t had a chance to produce AAVs yet as lab work was halted due to the COVID-19 pandemic.

“Without API, I would be a lot further behind in my master’s than what I am know,” says Henrickson. “It would have been a very steep learning curve figuring out how to produce the AAVs on my own. With the help of API sending me to Caltech to learn, I think it’s going to make things a lot smoother when I finally do start.”

API is a non-profit organization based in Edmonton that partners with industry, supports researchers and startups, and helps students bring their research into the world.

UNews - Amy Henrickson

U of L master’s student helps develop a better way to measure drug loading, enhance vaccine efficacy

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Early research opportunities lead to publications for U of L students

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Partnership gives U of L student one-of-a-kind learning opportunity

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