CAREER: Robust heterochiral molecular computing in mammalian cells
Project abstract
The DNA double helix is one of the most iconic and well-known molecular structures. All naturally occurring DNA double helices twist in the same direction: to the right. These are called D-DNA. Molecular devices made from D-DNA can interact directly with naturally occurring nucleic acids, but such devices are easily recognized and degraded by cellular defenses that recognize naturally occurring D-DNA. A wide range of D-DNA molecular sensors, circuits and actuators have been developed in recent years, but their utility in living cells and organisms is limited by this issue.
This CAREER project will enhance the practical utility of DNA-based molecular devices by engineering systems that include mirror-image "left-handed" DNA (L-DNA). The L-DNA double helix twists in the opposite direction to D-DNA and can therefore resist degradation in the cellular environment. In particular, this project will study the transmission of molecular information between L-DNA and D-DNA in these novel circuit designs, combining experimental and computational research to optimize the behavior of these systems and to demonstrate their use for sensing and control of biological systems. Preliminary data on this topic was published in ACS Synthetic Biology.
This CAREER project will also strengthen the biotechnology educational pipeline in New Mexico via a collaboration with ¡Explora!, a hands-on science museum in Albuquerque, NM. This collaboration will develop biotechnology minicourses for local high school students, with a focus on members of underrepresented groups. This project will thus enhance the scientific and engineering training infrastructure in the state of New Mexico.
Project news
August 2024Dr. Lakin is PI of a newly awarded pilot grant from UNM Rainforest Innovations on controlling cellular behavior using heterochiral DNAzymes.
July 2024A new undergraduate student, Abigail Carlson, joins the group. Welcome!
July 2024The third iteration of our NSF CAREER-funded biotechnology summer camp concludes! Two groups of high-school students from the Albuquerque area and a group of students recruited from across the country by the Air Force Research Lab each spent five days at ¡Explora! where they carried out experiments including cell-free expression of fluorescent proteins, agar art, and CRISPR interference reactions!
February 2024A new graduate student, Anshika Mishra, joins the group. Welcome!
October 2023Dr. Lakin is PI of a newly awarded grant: NSF grant 2312215: Simulation-guided design of heterochiral DNA nanostructures for biomaterials applications.
September 2023Dr. Tracy Mallette presents a poster on her work on heterochiral DNA computing in living mammalian cells at the 29th International Conference on DNA Computing and Molecular Programming at Tohoku University, Japan.
July 2023The second iteration of our NSF CAREER-funded biotechnology summer camp concludes! Two groups of high-school students from the Albuquerque area each spent five days at ¡Explora! working with Lakin Lab members carrying out activities and assays including cell-free expression reactions, bacterial transformations, and CRISPR interference experiments!
May 2023Dr. Lakin gives a talk and presents a poster at the SynCell 2023 conference at the University of Minnesota.
May 2023Tracy Mallette has successfully defended her PhD dissertation for the Biomedical Engineering program, entitled "Heterochiral DNA Nanotechnology for Biomedical Applications." She passed the defense with distinction. Congratulations Dr. Mallette!
May 2023Tracy Mallette wins the UNM School of Engineering's Outstanding Graduate Student Award for the combined Interdisciplinary Programs (Biomedical Engineering, Nanoscience & Microsystems Engineering, and Optical Science & Engineering). Congratulations!
October 2022Tracy Mallette wins a Poster Award at the 18th Annual Meeting of the Oligonucleotide Therapeutics Society. Congratulations!
August 2022Tracy Mallette is voted 1st runner-up for the DNA28 Best Student Presentation Award for her talk entitled "Protecting heterochiral DNA nanostructures against exonuclease-mediated degradation." Congratulations!
June 2022The first iteration of our NSF CAREER-funded biotechnology summer camp concludes! High-school students from the Albuquerque area spent four days at ¡Explora! working with Lakin Lab members carrying out activities and assays including cell-free expression reactions, gel electrophoresis, and CRISPR interference experiments!
June 2022Tracy Mallette's paper on using L-DNA to protect molecular circuits from degradation is published online in ACS Synthetic Biology. Congratulations!
November 2021Dr. Caroline Rempe joins the group as a technical staff member working on outreach projects. Welcome!
August 2021Dr. Lakin gives an invited talk as part of the Build-A-Cell virtual seminar series.
August 2021A new undergraduate student, Sameen Jawadi, joins the group. Welcome!
July 2021Dr. Lakin gives an invited talk at the Synthetic Approaches to Biology and Artificial Intelligence (SB-AI) workshop, a satellite workshop of the 2021 ALIFE conference.
May 2021Dr. Lakin gives an invited talk at the 2021 International Conference on Engineering Synthetic Cells and Organelles.
April 2021This CAREER project is formally underway!
March 2021Dr. Lakin's NSF CAREER award is featured on the UNM Newsroom website.
Project publications
2024
Tracy L. Mallette, Diane S. Lidke, and Matthew R. Lakin. Heterochiral modifications enhance robustness and function of DNA in living human cells. ChemBioChem, volume 25, number 5, e202300755, 2024. Link to article. BibTeX.
2022
Tracy L. Mallette and Matthew R. Lakin. Protecting heterochiral DNA nanostructures against exonuclease-mediated degradation. ACS Synthetic Biology, volume 11, number 7, pages 2222–2228, 2022. Link to article. BibTeX.
Outreach activities
July 2024 - Biotechnology summer camp
From June 17-21 and July 8-19, a total of 32 high-school students take part in our NSF-funded biotechnology summer camp over a total of three weeks. This was led by members of the Lakin Lab in collaboration with ¡Explora!. The first two weeks were reserved solely for students from the local Albuquerque area, while the third week was hosted in conjunction with the Air Force Research Lab summer program and included students from across the United States. Students carried out a range of experiments including bacterial transformations, cell-free expression and CRISPR interference assays, and agar art using fluorescent E. coli. The students also learned about basic molecular biology, biotechnology tools and lab techniques, and career options. Thank you to all lab members and ¡Explora! staff for their assistance, and to the students themselves! This was the second year in which attendance at this summer course doubled from the previous year!
July 2023 - Biotechnology summer camp
From July 10-21, 15 high-school students took part in an NSF-funded biotechnology summer camp over a two-week period, led by members of the Lakin Lab in collaboration with ¡Explora!. The first week was reserved solely for students from the local Albuquerque area, while the second week was hosted in conjunction with the Air Force Research Lab summer program and included students from across the United States. Students carried out experiments including cell-free expression assays, bacterial transformations, agar art using fluorescent E. coli, and cell-free CRISPR interference experiments. The students learned about biotechnology tools, lab techniques, and career options. Thank you to all lab members and ¡Explora! staff for their assistance, and to the students themselves!
June 2022 - Biotechnology summer camp
From June 27-30, seven high-school students from the Albuquerque area took part in an NSF-funded biotechnology summer camp led by members of the Lakin Lab in partnership with ¡Explora!, an experiential science museum located in Albuquerque. Students learned about biotechnology career options and carried out experiments and learning activities designed to teach biotechnology lab skills. These included cell-free protein expression reactions, agar art using strains of E. coli expressing fluorescent proteins and chromoproteins, gel electrophoresis, and cell-free CRISPR interference experiments. Thank you to all lab members and ¡Explora! staff for their assistance, and to the students themselves!
Project people
Dr. Matthew Lakin (Principal investigator)
- B.A., University of Cambridge, Computer Science, 2005
- Ph.D., University of Cambridge, Computer Science, 2010
- Associate Professor, Department of Computer Science
- Associate Professor (by courtesy), Department of Chemical & Biological Engineering
- Curriculum Vitae • Google Scholar page
Anshika Mishra (Graduate student)
- M.Sc., University of Pune, Biotechnology, 2019
- M.Tech., Indian Institute of Technology Jodhpur, Bioscience and Bioengineering, 2022
- Working towards: Ph.D. in Biomedical Engineering
Abigail Carlson (Undergraduate student)
- Working towards: B.S. in Computer Science and Biology
Dr. Caroline Rempe (Technical staff)
- B.S., University of New Mexico, Biology, 2010
- B.A., University of New Mexico, English, 2010
- Ph.D., University of Tennessee, Biology, 2016
Project alumni
Dr. Tracy Mallette
- Graduate student, 2018-2023
- Graduated with a Ph.D. in Biomedical Engineering, 2023
- Currently a postdoctoral researcher at the University of Washington
Sameen Jawadi
- Undergraduate student, 2021-2022
- Graduated summa cum laude with a B.A. in Biology in 2023