UCLA MAE Associate Professor Elisa Franco has received three new grants:

  • A three-year NSF award ($720k);
  • A one-year award from the Broad Stem Cell center at UCLA ($250k, shared with 2 coPIs in the medical school);
  • A UCOP grant that will support 2 summer exchange students from Howard University (HBCU) in 2021.

NSF grant – 2020039, total $720,000 over 3 years.

Project title BBSRC-NSF/BIO: “Characterizing efficiency and limitations of RNA regulators to achieve robust dynamic behaviors”.

This is a collaborative US/UK project is supported by the US National Science Foundation and the UK Biotechnology and Biological Sciences Research Council.

Co-PI in the UK – Francesca Ceroni, Imperial College London.

ABSTRACT – Advances in cell-based bioproduction (within engineered or synthetic cells) promises to solve global challenges such as production of fuel, food, cosmetics, and drugs in a sustainable manner. Scaling-up cellular bioproduction is however limited by the burdens this can cause to the host cell. This research will develop tunable, low-burden RNA molecules for control of gene expression of useful molecules. Experiments will be supported by computational models, to understand the dynamics of cellular burden and to optimize bioproduction performance. This project, which is a collaboration between researchers at the University of California-Los Angeles (US) and Imperial College London (UK), will provide training and mentorship to several graduate and undergraduate students. Results and methods will be shared with the scientific community via publications, archival documents, and data repositories; the Principal Investigators will also share their work within the World Economic Forum Expert Network and the Engineering Biology Research Consortium. This research will be integrated both in graduate courses and in the Cold Spring Harbor Laboratory Synthetic Biology summer course. Dr. Franco will deliver outreach talks at underserved schools in California’s Inland Empire as well as at international conferences supported by the IEEE Controls Systems Society.

Synthetic biology has made it possible to repurpose cells to operate as microscale factories, energy sources, and even computers. However, the introduction of pathways that are poorly tunable and non-native to the host often causes undesired cross-interactions and unpredictable responses, and reliable engineering of cells remains a challenge. In particular, the introduction of exogenous pathways depletes cellular resources of the host, triggering physiological changes, lower growth, and poor circuit performance, a set of phenomena collectively known as cellular burden. This research will address the challenges related to robust circuit engineering and burden mitigation by developing synthetic RNA-based regulators, a programmable platform that imposes a low burden on the host. The project will focus on systematic screening and tuning of the response function of two classes of RNA regulators, which will then be used to characterize the kinetics of the cellular burden response, whose onset and recovery speed have not been elucidated. An improved knowledge of burden kinetics will enable the generation of robust RNA-based feedback loops to manage bioproduction of mevalonic-acid in E. coli. At every stage, experiments will be supported and guided by mathematical modeling and feedback control design principles.

Rose Hills Foundation Innovator Grant, $250k over 1 year – UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

Project title “Development of RNA-aptamers for live cell imaging in embryonic stem cells”.

Co PIs – Prof. Kathrin Plath (Biological Chemistry) and Prof. Douglas Black (Microbiology, Immunology & Molecular Genetics).

ABSTRACT – Live cell imaging is one of the most important tools for studying cell behaviors that drive stem cell decisions, embryonic development and tissue formation. Typically, genetically-encoded reporters are expressed under cell type-specific cis-regulatory elements to drive fluorescent protein expression for visualization in living cells. Yet, this approach requires extensive cell line engineering and therefore is limited in its scalability. Similarly, when imaging RNA, complicated methods that involve various parts and targeting approaches are needed. Here, we will address this challenge by developing a new method for tracking individual RNA molecules inside living cells. Building on recent advances in nucleic acids nanotechnology, we will engineer RNA aptamers that switch conformation, assemble, and fluoresce upon hybridization to the desired target. Relative to fluorescent proteins, a major advantage of RNA aptamers is that their secondary structure, function, and kinetics are programmable via sequence design. In addition, these RNA aptamers can be targeted to specific transcripts by simply taking advantage of RNA-RNA hybrid formation. Yet, a challenge in using fluorogenic aptamers for tracking RNA molecules in living cells is that several aptamer copies need to be recruited to the target RNA to generate sufficient brightness. Moreover, a low fluorescent background (high signal-to noise ratio) is essential to specifically detect RNAs even when lowly expressed, which ideally requires that the aptamer only fluoresces upon binding to the target RNA. Here, we will pursue two approaches to reduce background fluorescence and increase the signal to noise ratio for RNA imaging in mammalian cells with immediate applicability to live cell imaging of any RNA of interest and for cell isolation based on the presence of specific RNA molecules. Our team brings together several investigators with complementary expertise (Elisa Franco – RNA engineering, Kathrin Plath – stem cell biology, Doug Black – RNA biology).

University of California-Historically Black Colleges and Universities Initiative (UC-HBCU).

Project title “UCLA-Howard University Summer Exchange – Engineering artificial biopolymers”.

PI at Howard University, Prof. Preethi Chandran (Department of Chemical Engineering).

OVERVIEW – This project aims to support two undergraduate students from the Department of Chemical Engineering at Howard University to spend 10 weeks doing research in the Mechanical and Aerospace Engineering at UCLA during Summer 2021. These summer research experiences will help initiate an interdisciplinary collaboration between the PIs, with the long-term goal of establishing a sustained partnership between their departments and increase enrollment of underrepresented students in UC graduate programs. During the summer program, students will be mentored by Prof. Franco and her team, and receive support from Prof. Chandran during the academic year, before, during, and after the exchange. This UC-HBCU project will provide financial support as well as engage participating students in a variety of summer activities at UCLA. The students will conduct cutting-edge interdisciplinary research aimed to build models of synthetic DNA nanostructures that have relevance in materials science and nanotechnology.