Maureen McKeague | McGill University (original) (raw)
Uploads
Papers by Maureen McKeague
Nature Reviews Methods Primers, Jul 20, 2023
McGill Science Undergraduate Research Journal, Mar 26, 2023
Sensing small molecules, including drugs and their metabolites inside cells, is critical for drug... more Sensing small molecules, including drugs and their metabolites inside cells, is critical for drug discovery and development, diagnostics, and precision medicine. To facilitate sensitive, long-term studies of drug uptake in cultured cells and animals, we developed a genetically-encoded aptamer biosensor platform for non-invasive real-time measurements of drug distribution. We combined the high specificity of aptamer molecular recognition with the easy-to-detect properties of fluorescent proteins. We tested six different aptamer biosensors, showcasing the platform versatility. The biosensors display high sensitivity and specificity for detecting their specific drug target over related analogs. Furthermore, the biosensor responses were dose dependent and could be detected in individual live cells. We designed our platform for easy integration into animal genomes; thus, we incorporated one aptamer biosensor into zebrafish, an important model vertebrate. The biosensor was stably expresse...
McGill Science Undergraduate Research Journal, Apr 8, 2022
Nature Reviews Methods Primers
The 4th annual symposium of the International Society on Aptamers, Aptamers 2017, was held in Oxf... more The 4th annual symposium of the International Society on Aptamers, Aptamers 2017, was held in Oxford on the 11th and 12th April and was well attended, with presenters from Europe (Spain, Germany, Austria, and UK), North and South America, Asia, and Australasia presenting on a diverse range of topics, from enhancing SELEX, to diagnostic applications such as lateral flow devices or medical imaging, to therapeutic applications such as drug delivery. The conference was split into six sections in total, covering chemical modifications, disease, analysis/diagnostics, tools/selection/design, riboswitches, and computation with over 50 oral and poster presentations. The conference started with a welcome from both the Symposium Chair, Professor Dr Ulrich Hahn (University of Hamburg, Germany) and the President of the International Society on Aptamers, Dr Sarah Shigdar (Deakin University, Australia). CHEMICAL MODIFICATIONS OF APTAMERS Aptamers are developing for a number of applications and the...
Polymers with sequence definition allow access to programmable morphologies and applications, but... more Polymers with sequence definition allow access to programmable morphologies and applications, but directly correlating polymer structure to function currently requires case-by-case analysis: high throughput methods that identify promising species from entire chemical families are required. Here, we show that the discovery of effective protein target-recognition molecules can be achieved using DNA-encoded libraries of chemically diverse sequence-defined oligomers, generated on an automated DNA synthesizer. These structures are ALENOMERs – Aptamer-Like ENcoded OligoMERs – that are read and sequenced using a DNA code that branches from, and corresponds to, the target-binding oligomer. By incorporating nucleosidic and non-nucleosidic components into alenomers at specific locations, we unlock new supramolecular interactions for biomolecule binding, and directly correlate their effectiveness at each site. Our alenomer library screening removes the low throughput bottleneck of analyzing in...
Contemporary Educational Psychology, 2022
base to describe aptamers and SELEX experiments
Aptamer base: a collaborative knowledge base to describe aptamers and SELEX experiments
Computational approaches toward the design of pools for the in vitro selection of complex aptamers
Nucleic acid aptamers are unique molecular structures used for binding to diverse targets. There ... more Nucleic acid aptamers are unique molecular structures used for binding to diverse targets. There is a major challenge in adapting in vitro-selected RNA aptamers for building in vivo RNA devices that control cell function. In contrast, their natural nucleic acid counterparts, riboswitches, were deliberately evolved for efficient gene regulation and cellular programming. Encoded within cells, riboswitches exploit a natural aptamer module to bind to an intracellular small molecule target enabling regulation of fundamental metabolic pathways. Here, we review several key features of natural riboswitches that may account for their function in the cellular environment. We compared these features to those of in vitro selected RNA aptamers that bind to small molecule targets. Our analysis revealed that the aptamer structure and magnesium-dependence might be the largest contributors to failed synthetic RNA devices. Thus, we make several suggestions for forthcoming aptamer selections, which ma...
Journal: RSC AdvancesPaper: c3ra43893gTitle: Development of nucleic acid probes capable of direct... more Journal: RSC AdvancesPaper: c3ra43893gTitle: Development of nucleic acid probes capable of direct and selective homocysteine detection in human serumEditor's queries are marked like this... 1 , and for your convenience line numbers are inserted like this... 5Please ensure that all queries are answered when returning your proof corrections so that publication of yourarticle is not delayed.QueryReferenceQuery Remarks1For your information: You can cite this article before youreceive notication of the page numbers by using thefollowing format: (authors), RSC Adv., (year), DOI: 10.1039/c3ra43893g.2Please carefully check the spelling of all author names. Thisis important for the correct indexing and future citation ofyour article. No late corrections can be made.3 Ref. 26: Please provide the page (or article) number(s).4Please check that the GA text ts within the allocated spaceindicatedonthefront page oftheproof. Iftheentrydoesnottbetweenthetwo horizontallines,thenpleasetrimthetex...
ACS Pharmacology & Translational Science, 2021
Aptamers for Analytical Applications, 2018
Metabolic Engineering, 2016
Nucleic Acids Research, 2016
SUMMARYFor nearly 50 years, translational research studies aimed at improving chemotherapy-induce... more SUMMARYFor nearly 50 years, translational research studies aimed at improving chemotherapy-induced killing of cancer cells have focused on the induction of apoptosis. Here we show that a PARP-1-mediated programmed cell death mechanism “parthanatos” is associated with the successful, front-line treatment of a common cancer. Peripheral blood mononuclear cells (PBMCs) from healthy human donors (10 of 10 tested), as well as primary cancer cells from approximately 50% of acute myeloid leukemia (AML) patients (n = 18 of 39 tested, French-American-British (FAB) subtypes M4 and M5) exhibited two distinctive features of parthanatos upon treatment with a front-line drug combination of cytarabine and an anthracycline. Statistically significant improvements in survival rates were observed in the parthanatos positive versus parthanatos negative AML patient groups (HR = 0.22 – 0.38, p = 0.002 – 0.05). Near-median expression of PARP1 mRNA was associated with a 50% longer survival time (HR = 0.66, ...
Nature Reviews Methods Primers, Jul 20, 2023
McGill Science Undergraduate Research Journal, Mar 26, 2023
Sensing small molecules, including drugs and their metabolites inside cells, is critical for drug... more Sensing small molecules, including drugs and their metabolites inside cells, is critical for drug discovery and development, diagnostics, and precision medicine. To facilitate sensitive, long-term studies of drug uptake in cultured cells and animals, we developed a genetically-encoded aptamer biosensor platform for non-invasive real-time measurements of drug distribution. We combined the high specificity of aptamer molecular recognition with the easy-to-detect properties of fluorescent proteins. We tested six different aptamer biosensors, showcasing the platform versatility. The biosensors display high sensitivity and specificity for detecting their specific drug target over related analogs. Furthermore, the biosensor responses were dose dependent and could be detected in individual live cells. We designed our platform for easy integration into animal genomes; thus, we incorporated one aptamer biosensor into zebrafish, an important model vertebrate. The biosensor was stably expresse...
McGill Science Undergraduate Research Journal, Apr 8, 2022
Nature Reviews Methods Primers
The 4th annual symposium of the International Society on Aptamers, Aptamers 2017, was held in Oxf... more The 4th annual symposium of the International Society on Aptamers, Aptamers 2017, was held in Oxford on the 11th and 12th April and was well attended, with presenters from Europe (Spain, Germany, Austria, and UK), North and South America, Asia, and Australasia presenting on a diverse range of topics, from enhancing SELEX, to diagnostic applications such as lateral flow devices or medical imaging, to therapeutic applications such as drug delivery. The conference was split into six sections in total, covering chemical modifications, disease, analysis/diagnostics, tools/selection/design, riboswitches, and computation with over 50 oral and poster presentations. The conference started with a welcome from both the Symposium Chair, Professor Dr Ulrich Hahn (University of Hamburg, Germany) and the President of the International Society on Aptamers, Dr Sarah Shigdar (Deakin University, Australia). CHEMICAL MODIFICATIONS OF APTAMERS Aptamers are developing for a number of applications and the...
Polymers with sequence definition allow access to programmable morphologies and applications, but... more Polymers with sequence definition allow access to programmable morphologies and applications, but directly correlating polymer structure to function currently requires case-by-case analysis: high throughput methods that identify promising species from entire chemical families are required. Here, we show that the discovery of effective protein target-recognition molecules can be achieved using DNA-encoded libraries of chemically diverse sequence-defined oligomers, generated on an automated DNA synthesizer. These structures are ALENOMERs – Aptamer-Like ENcoded OligoMERs – that are read and sequenced using a DNA code that branches from, and corresponds to, the target-binding oligomer. By incorporating nucleosidic and non-nucleosidic components into alenomers at specific locations, we unlock new supramolecular interactions for biomolecule binding, and directly correlate their effectiveness at each site. Our alenomer library screening removes the low throughput bottleneck of analyzing in...
Contemporary Educational Psychology, 2022
base to describe aptamers and SELEX experiments
Aptamer base: a collaborative knowledge base to describe aptamers and SELEX experiments
Computational approaches toward the design of pools for the in vitro selection of complex aptamers
Nucleic acid aptamers are unique molecular structures used for binding to diverse targets. There ... more Nucleic acid aptamers are unique molecular structures used for binding to diverse targets. There is a major challenge in adapting in vitro-selected RNA aptamers for building in vivo RNA devices that control cell function. In contrast, their natural nucleic acid counterparts, riboswitches, were deliberately evolved for efficient gene regulation and cellular programming. Encoded within cells, riboswitches exploit a natural aptamer module to bind to an intracellular small molecule target enabling regulation of fundamental metabolic pathways. Here, we review several key features of natural riboswitches that may account for their function in the cellular environment. We compared these features to those of in vitro selected RNA aptamers that bind to small molecule targets. Our analysis revealed that the aptamer structure and magnesium-dependence might be the largest contributors to failed synthetic RNA devices. Thus, we make several suggestions for forthcoming aptamer selections, which ma...
Journal: RSC AdvancesPaper: c3ra43893gTitle: Development of nucleic acid probes capable of direct... more Journal: RSC AdvancesPaper: c3ra43893gTitle: Development of nucleic acid probes capable of direct and selective homocysteine detection in human serumEditor's queries are marked like this... 1 , and for your convenience line numbers are inserted like this... 5Please ensure that all queries are answered when returning your proof corrections so that publication of yourarticle is not delayed.QueryReferenceQuery Remarks1For your information: You can cite this article before youreceive notication of the page numbers by using thefollowing format: (authors), RSC Adv., (year), DOI: 10.1039/c3ra43893g.2Please carefully check the spelling of all author names. Thisis important for the correct indexing and future citation ofyour article. No late corrections can be made.3 Ref. 26: Please provide the page (or article) number(s).4Please check that the GA text ts within the allocated spaceindicatedonthefront page oftheproof. Iftheentrydoesnottbetweenthetwo horizontallines,thenpleasetrimthetex...
ACS Pharmacology & Translational Science, 2021
Aptamers for Analytical Applications, 2018
Metabolic Engineering, 2016
Nucleic Acids Research, 2016
SUMMARYFor nearly 50 years, translational research studies aimed at improving chemotherapy-induce... more SUMMARYFor nearly 50 years, translational research studies aimed at improving chemotherapy-induced killing of cancer cells have focused on the induction of apoptosis. Here we show that a PARP-1-mediated programmed cell death mechanism “parthanatos” is associated with the successful, front-line treatment of a common cancer. Peripheral blood mononuclear cells (PBMCs) from healthy human donors (10 of 10 tested), as well as primary cancer cells from approximately 50% of acute myeloid leukemia (AML) patients (n = 18 of 39 tested, French-American-British (FAB) subtypes M4 and M5) exhibited two distinctive features of parthanatos upon treatment with a front-line drug combination of cytarabine and an anthracycline. Statistically significant improvements in survival rates were observed in the parthanatos positive versus parthanatos negative AML patient groups (HR = 0.22 – 0.38, p = 0.002 – 0.05). Near-median expression of PARP1 mRNA was associated with a 50% longer survival time (HR = 0.66, ...