What is happening at the Li Lab? – Research topics summed up

Hi!

As you can see on the website under “Research“, we specialize in DNAzymes and aptamers, or more broadly, functional nucleic acids (FNAs). There, you can also learn a bit more about what these actually are. Within our research group, different people work on different targets for FNAs. We thought we’d sum them up for you to get a nice overview 🙂

Within our group, we aim to develop FNAs for use in diagnostics. This includes different targets from bacteria, to viruses, and more.

Bacterial targets include Campylobacter, Fusobacterium nucleatum, Clostridium difficile, and Treponema pallidum (cause of syphilis).

Campylobacter is one of four key global causes of diarrhoeal disease. It is considered to be the most common bacterial cause of human gastroenteritis in the world.

Fusobacterium nucleatum is associated with many poor health conditions such as gum disease, adverse pregnancy outcomes, and colorectal cancer. More recently, it has also been linked to endometriosis.

Clostridium difficile is a bacterial species that causes infection of the colon. Serious infection may lead to hospitalization. C. difficile infection can be spread easily and is difficult to diagnose. It is often diagnosed by looking at the symptoms and culturing of the bacteria, but this method is time-consuming and inaccurate.

Treponema pallidum is the species of bacteria which causes syphilis, a sexually transmitted infection which has been on the rise in recent years. Current diagnostics measure antibodies produced in response to syphilis infection as Treponema pallidum is difficult to culture.

In addition to bacteria, our FNAs also target viruses. Viral targets include SARS-CoV-2, norovirus, and influenza.

SARS-CoV-2, and the resulting COVID-19 disease, has thrown our world into a pandemic at the end of 2019, resulting in 6 million deaths so far. Many variants of the virus have arisen overtime, making vaccination and detection more challenging.

Norovirus is the cause of over 50% of foodborne illnesses in the U.S. Infection with the virus primarily results in vomiting and diarrhoea. Norovirus illness brings a large disease burden as it is estimated to cost $60 billion worldwide due to healthcare costs and lost productivity.

Influenza virus, more commonly known as the flu virus, causes respiratory illness, infecting the nose, throat, and sometimes the lungs. Diagnosis of the flu is most commonly based on symptoms. One challenge of diagnosing influenza through diagnostic testing is the existence of many influenza subtypes.

On top of that, we have some people working on pancreatic cancer, malignant hyperthermia, and the conservation of species

Pancreatic cancer is a cancer which is rarely diagnosed in the early stages as symptoms only develop once the cancer has metastasized to other organs. Therefore, the 5-year survival rate of pancreatic cancer is shockingly low, at around 12.5%. Earlier diagnosis of pancreatic cancer would improve patients’ chances of remission.

Malignant hyperthermia is a severe reaction that can occur in response to medication used for general anesthesia. Symptoms include an increase in heart rate, body temperature, and muscle rigidity. If left untreated, malignant hyperthermia can be fatal. Currently, diagnosis of malignant hyperthermia relies on the response of biopsy samples to the different drugs. A less invasive method with decreased turn-around time using FNAs is desired.

Conservation of species is important for maintaining ecosystems, as each species occupies its own niche in that ecosystem. Disappearance of a species can have disastrous effects on the ecosystem itself. In the Li Lab, the focus is on the conservation of caribou, a large species of reindeer. The intervention of humans through oil and gas exploration in Alberta has led to a decrease in caribou habitat, in turn leading to a decrease in caribou. Monitoring caribou in the environment can indicate the success or failure of intervention to restore caribou habitat. By designing an FNA-based test, we hope to monitor the caribou species in the field and help efforts in the conservation of the caribou species.

So, these are the different things we’re working on in the Li Lab. The final goal of the majority of these projects is the development of point-of-care tests which serve to improve pitfalls of current tests. These include invasiveness, high turn-around time, and costs. We hope it made some things a bit clearer, and that it’s piqued your interest for what we’re doing around here!

Halloween Contest Costume Winners

Back in October 2023, our department had a costume contest for Halloween. Of course, we had to go with Barbie in the Lab.

We weren’t the only ones with a Barbie-themed costume, but with a lot of work from the wonderful undergraduate students within the lab, we pulled out the win.

Our prize? 🍕 Lunch paid by the department 🙂

Hi Barbie 👋

Aptamers for protection against viral infections

The Li Lab, in collaboration with the Miller Lab, has made progress with using aptamers as therapeutics to prevent infections like COVID-19.

A high binding affinity COVID-19 (C19HBA) aptamer was compared to commercial monoclonal antibodies in a pre-clinical study. Results show that testing has been successful in protected the mouse model used in the pre-clinical study from infection as effectively as commercial monoclonal antibodies.

For the story published by McMaster University, click HERE.

The aptamer research described above is partially funded by Zentek Ltd., a technology development and commercialization company. We’re thankful for the collaboration with both the Miller Lab and Zentek Ltd.

For a news release by Zentek Ltd. on initial testing, click HERE.

For a news release by Zentek Ltd. on the aptamer technology platform, click HERE.

For a news release by Zentek Ltd. on the results of the pre-clinical study, click HERE.

New DNAzyme that requires an organic solvent!

Read about our latest RNA-cleaving DNAzyme, one that requires an organic solvent to function!  

Given that many organic molecules are widely used as solvents in synthetic and analytical chemistry, we were motivated to derive a functional DNAzyme in these conditions. While several DNAzymes in literature have been reported to work under organic conditions, no prior study has ever selected for DNAzymes that strictly require an organic solvent to function.  

In this study, using a positive selection in dimethyl sulfoxide (DMSO) and a negative selection in an aqueous solution, we isolated an RNA-cleaving DNAzyme that strictly requires DMSO for its catalytic activity. A minimized, more efficient version of the DNAzyme was then generated, and applied in a proof-of-concept aptazyme system for sensing applications.  

Overall, we continue to be fascinated by the amazing capabilities of in vitro selection and catalytic DNA! Check out the full paper HERE.

Fluorogenic DNAzyme for F. nucleatum detection

Check out our latest DNAzyme, DT4, a trans-acting DNAzyme that can be activated by a thermally stable protein target which is unique to Fusobacterium nucleatum subspecies.

Our interest in detecting this human pathogenic bacterium resides with the fact that F. nucleatum is associated with many poor health conditions, such as gum disease, adverse pregnancy outcomes, and colorectal cancer.

Our efforts in demonstrating that DT4 can function as a fluorescent sensor in both human saliva and stool samples provides the opportunity to develop diagnostic platforms for F. nucleatum since thermally stable targets overcome the nuclease activity in biological samples.

Click HERE for the full paper.

On the Cover

A research article first published in February 2023 on the characterization of diverse DNA aptamers for recognition of COVID-19 has been featured on the cover of the most recent issue (issue #5) of the journal Analysis & Sensing.

We’re all very excited and overjoyed with the recognition of all the hard work that’s being done here in the lab.

For the full article, check out the following link:

Comparative Characterization of Diverse DNA Aptamers for Recognition of Spike Proteins of Multiple SARS-CoV-2 Variants

For more papers, see the Publications page of the website.

Congratulations to Dr. Shuwen Qian!

Shuwen successfully defended her thesis a couple of weeks ago which means that she is close to receiving her actual piece of paper certifying she has completed her PhD!

Some thoughts of Shuwen on her PhD journey:

Doing a PhD IS challenging, even beyond what I had imagined five years ago when I started this journey. This road trip, which I expected to have ups and downs and go back and forth, sure was a rollercoaster. If I am honest, most of the time (for me) was more of a down and back experience. However, I was fortunate enough to find my way out of those downs and back into some ups with incredible help and support of my supervisors, other lab members, and peers. It has been such a long way that it felt quite surreal that I made it to the point where I got to defend my PhD thesis, and it didn’t even feel real yet when we were all gathered at the Phoenix for my defence celebration. I feel truly blessed for this achievement and am beyond proud of myself. I chose to stay strong, to stick through it and make things happen. There’s definitely a weight off my shoulders now and I’m feeling so free, which I wish to be in the rest of my life also: To be free, always.

It’s true that a PhD isn’t an easy journey, but it’s supposed to shape you into a better scientist. We are all incredibly proud of the scientist Shuwen has become throughout the years and we look forward to see what’s next for her!

Summer Scholars Program

The Biochemistry & Biomedical Sciences Summer Scholars Program (SSP) is a 12 week immersive research and mentorship program awarded to 9 undergraduate scholars this year for the second time since its establishment. I have had the pleasure of joining The Li lab through the SSP in May of 2023. Under the direct mentorship of Dr. Li & Jim Gu, my project focused on investigating DNAzyme activity in the cleavage of a specific RNA modification.

This experience not only allowed me to understand and support ongoing research efforts, yet also see first hand the true humanity behind all the research done in The Li lab and McMaster’s Biochemistry & Biomedical Sciences Department. As an undergraduate student now entering my second year in the Honours Biochemistry program here at McMaster, the ability to connect with other like minded undergraduate students, graduate students, post doctoral fellows, faculty members and research staff, is truly unparalleled to anything I have experienced before.

I am continuously grateful for this opportunity and the chance to connect with so many talented, kind, as well as genuine people this past summer.

~ Tegvir S. Grewal

A wonderful lab retreat – Four days of happiness and relaxation

In July, I brought students and staff of my laboratory to Blue Mountain for a lab retreat. We had 22 people join in the fun, but unfortunately 7 couldn’t make it. We spent the days making breakfast and lunch ourselves, and we visited local restaurants two evenings for dinner. The final night was Taco Night, and we prepared dinner ourselves. Arguably the best dinner of all the days.

We played games, sang songs, and did various sports activities including volleyball, tennis, basketball, golf, running, hiking, and beach volleyball. The days of the retreat were filled with joy, relaxation, singing, and friendship, and I have fully appreciated the hobbies and talents of the students outside of science. It turns out that my lab has amazing athletes, singers, organizers, cooks, storytellers, and comedians.

They can work hard and play hard, and are just an amazing group of lovely young people. Even though everyone comes from all over the world with different backgrounds, everyone has a kind and beautiful heart and a willingness to help others.

I couldn’t be more honoured and proud to have such a very happy, kind, and helpful laboratory family. This trip not only allowed me to get to know them better, but it also allowed everyone to strengthen their friendships.

Money and time well spent for a priceless memory that we’ll all carry with us. Couldn’t be happier with the current team and dynamics that we have going in our lab!

– Dr. Yingfu Li

Salmonella Detection

Learn about the lab’s recent work on the detection of Salmonella for food safety here https://brighterworld.mcmaster.ca/articles/salmonella-solution-researchers-develop-rapid-test-for-food-contamination/

Angewandte Chemie International Edition has a Press Release for this work:

https://onlinelibrary.wiley.com/page/journal/15213773/homepage/press/202315press.html.

CTV news report our story, “McMaster researchers develop salmonella solution”

https://www.ctvnews.ca/video?clipId=2669669.

Jiuxing Li, Shadman Khan, Jimmy Gu, Carlos D. M. Filipe*, Tohid F. Didar*, Yingfu Li*. A simple Au-on-Au colorimetric sensor for food-borne pathogen Salmonella typhimurium. Angew. Chem. Int. Ed. 2023, e202300828. (DOI: 10.1002/anie.202300828, IF: 16.8)

Jiuxing’s Editor Contributions

Congratulations to Jiuxing for his work as a guide editor and advisor for several journals.

He has served as a guest editor for Sensors and Frontiers in Chemistry, Sensors for special issue “Micro/Nano Biosensors and Devices”, Frontiers in Chemistry for Research Topic “Advanced Nanomaterials for in Vitro Diagnostics” and as a topical advisory panel member of sensors.

Aptamers for SARS-CoV-2: Isolation, Characterization, and Diagnostic and Therapeutic Developments

In this review, we are proud to share the incredible work done globally in developing aptamers for the COVID-19 pandemic. Given their desirable characteristics as molecular recognition elements, nucleic acid aptamers were of significant interest to multiple labs worldwide over the past few years. Our review paper features a comprehensive comparison between the most notable SARS-CoV-2 aptamers, taking a detailed look at the SELEX strategies, sequence alignments, secondary structures, and multimeric engineering achievements. We also highlight the application of these aptamers as ligands for therapeutic agents and biosensor development. Overall, aptamers represent a compelling solution to the diagnostic and therapeutic challenges of COVID-19, and we hope this review propels further aptamer research for current and future pandemics.
Read more about the paper here: https://doi.org/10.1002/anse.202200012

-Ryan

Nucleic-Acid-Based Electrochemical Biosensors for Clinical Applications

We are excited to announce our recent review paper on the use of nucleic acids in electrochemical biosensors in collaboration with the Dr. Soleymani lab. Nucleic acids have unique structural motifs that allow them to bind non-nucleic acid targets (aptamers) and catalyze chemical reactions (DNAzymes), making them excellent candidates for use in biosensors. This review paper highlights the historical evolution of nucleic acids as probes in electrochemical biosensors and provides specific examples of their use in clinical settings such as infectious disease, cancer, and cardiovascular health. DNA, in particular, has proven to be an ideal biorecognition element and redox reporter probe due to its ability to be easily modified with various functional groups. We hope that our review will serve as a valuable resource for researchers in the field of biosensors and contribute to the development of new diagnostic tools for a wide range of diseases. Read more about it here: https://doi.org/10.1002/anie.202212496

-Zijie

“Three on Three”

Read our latest work on SARS-CoV-2 detection in saliva, where we developed a trimeric aptamer, named TMSA52, for the recognition of SARS-CoV-2 spike protein. The aptamer not only possesses superb binding affinity but is also capable of binding several SARS-CoV-2 spike protein variants with picomolar affinity, as well as pseudotyped lentiviruses expressing SARS-CoV-2 spike protein variants with femtomolar affinity. Using Pd-Ir nanocubes as nanozymes in an enzyme-linked aptamer binding assay (ELABA), TMSA52 was capable of sensitively detecting diverse pseudotyped lentiviruses in pooled human saliva.  The ELABA was also used to test 50 SARS-CoV-2 positive and 60 negative patient saliva samples, providing sensitivity and specificity values of 84.0% and 98.3%, respectively, thus highlighting the potential of TMSA52 for the development of future rapid tests.

Jiuxing Li, Zijie Zhang, Jimmy Gu, Ryan Amini, Alexandria Mansfield, Jianrun Xia, Dawn White, Hannah D. Stacey, Jann C. Ang, Gurpreet Panesar, Alfredo Capretta, Carlos D. M. Filipe, Karen Mossman, Bruno J. Salena, Jonathan Gubbay, Cynthia Balion, Leyla Soleymani, Matthew S. Miller, Deborah Yamamura, John D. Brennan*, and Yingfu Li*. Three on three: Universal and high-affinity molecular recognition of the symmetric homotrimeric spike protein of SARS-CoV-2 with a symmetric homotrimeric aptamer. J. Am. Chem. Soc. 2022, 144, 23465–23473. (DOI: 10.1021/jacs.2c09870, IF: 16.38)

Discovery and translation of functional nucleic acids for clinically diagnosing infectious diseases: Opportunities and challenges

Read our recent review on the discovery and translation of functional nucleic acids developed in our lab.

Jiuxing Li§, Zijie Zhang§, Rudi Liu§, Ryan Amini, Bruno J. Salena, and Yingfu Li*. Discovery and translation of functional nucleic acids for clinically diagnosing infectious diseases: opportunities and challenges. TrAC, Trends Anal. Chem. 2023, 158, 116886 (DOI: 10.1016/j.trac.2022.116886, IF: 12.296)

A Universal Aptamer for SARS-CoV-2 Detection

We’re excited to share our latest work on SARS-CoV-2 where we expand on our previous publications and describe an aptamer class that binds all major variants of concern with high affinity. This is an important tool for the development of aptamer based COVID detection technologies that can be specific, sensitive and robust for the detection of current and possibly future variants. Read more about our work here. -Jim

Zhang Z, Li J, Gu J, Amini R, Stacey HD, Ang JC, White D, Filipe CDM, Mossman K, Miller MS, Salena BJ, Yamamura D, Sen P, Soleymani L, Brennan JD, Li Y. A Universal DNA Aptamer that Recognizes Spike Proteins of Diverse SARS-CoV-2 Variants of Concern. Chemistry. 2022 Feb 26:e202200524. doi: 10.1002/chem.202200524. Epub ahead of print. PMID: 35218097.

Aptamers from random sequence space: Accomplishments, gaps and future considerations

Aptamers are nucleic acids that are capable of recognizing target molecules. Over the past 30 years, thousands of aptamers have been discovered by scientists via in vitro selection technique. This review examined the range of targets as well as the affinity and specificity of ~1000 generated aptamers. By comparing the synthetic aptamers with natural riboswitches, protein-based recognition elements, a gap between synthetic aptamers and natural recognition elements was revealed.  A series of ideas for developing better aptamers were proposed to solve the real world problems. We hope these strategies can help aptamers remain high functionality in application environment. Happy reading 😊 – Shuwen Qian

Qian, S.; Chang, D.; He, S.; Li, Y. Aptamers from Random Sequence Space: Accomplishments, Gaps and Future Considerations. Analytica Chimica Acta 2022, 1196, 339511. https://doi.org/10.1016/j.aca.2022.339511

Applying our SARS-CoV-2 Aptamers for Diagnostics

Following up on our recent report of high-affinity DNA aptamers for SARS-CoV-2, we’ve been busy working with our collaborators in the Soleymani Lab and the Biointerfaces Institute to apply them on electrochemical sensors. Read our latest COVID19 paper at Pubmed to learn more about how we achieve high sensitivity detection of SARS-CoV-2 in unprocessed human saliva to pave the way for a rapid and sample diagnostic test.

Facile Synthesis of Pd-Ir Nanocubes for Biosensing

Take a quick look at our recent publication in Frontiers in Chemistry. In this paper, a simple and surfactant-free approach is presented to synthesize Pd-Ir nanocubes with atomic Ir shell thickness in an aqueous solution at room temperature. Biomolecules such as antibodies and nucleic acids have free access to the surface of Pd-Ir nanocubes. Applications of Pd-Ir nanocubes in immunoassays and aptamer-based biosensors are realized, exploiting the excellent peroxidase activity and fluorescence quenching ability of Pd-Ir nanocubes. Read more about our work at Pubmed. – Jiuxing

Li J, Li Y. Facile Synthesis of Pd-Ir Nanocubes for Biosensing. Front Chem. 2021 Nov 24;9:775220. doi: 10.3389/fchem.2021.775220. PMID: 34900937; PMCID: PMC8651546.

Welcome to Giulia Core

The Li Lab welcome our newest member, Giulia Core, who will be joining us as a visiting Ph.D. student from the University of Glasgow. She will be working on molecular diagnostic technologies.

DNA Aptamers for SARS-CoV-2

The Li Lab and our collaborators from across the McMaster community have published our first report on our novel aptamers for COVID19! The lab has refocused our efforts over the past year to address pressing COVID19 problems and we’re excited to finally be sharing our work. Read more about our work at Pubmed.

NSERC & L’OrĂ©al-UNESCO Women in Science and IUPAC Young Chemist

Li Lab postdoctoral fellow Erin McConnell has been awarded the NSERC & L’OrĂ©al-UNESCO Women in Science Supplement. Congratulations to Erin for her fantastic work as a scientist and as a role model for young scientists around the world.

Explore the following links to learn more about Erin’s work and the work of the other great researchers recently recognized.

Canadian Awarding ceremony of the L’OrĂ©al-UNESCO For Women in Science fellowships

NSERC and L’Oréal-UNESCO For Women in Science Supplement

L’Oréal-UNESCO For Women in Science 2018: Erin McConnell

IUPAC Young Chemist

https://iupac.org/100/pt-of-chemist/#erin-mcconnell-he

A DNAzyme Feedback Amplification Strategy for Biosensing

Take a look at this recent publication from the Li Lab in Angewandte Chemie International Edition. In this paper, we explore a novel signal amplification strategy termed DNAzyme feedback amplification (DFA). This method takes advantage of rolling circle amplification and RNA-cleaving DNAzymes for biosensing applications, with sensitivity improvements of 3-6 orders of magnitude when compared to conventional methods. -Suraj