Projects

MiRNA Response to Folic Acid during Embryogenesis and Development of Caenhorabditis elegans 


Abstract

Folic acid, a form of folate, is a common dietary supplement used in combination with other vitamins and minerals in prenatal vitamins during female human pregnancy. Folic acid has great importance in neurogenesis, epigenetic regulation, and DNA formation in many organisms, but can also be toxic at overly abundant levels [1]. Folic acid is metabolized into folate derivatives through the use of multiple enzymes in the folate cycle. Furthermore, the methionine cycle converges with the folate cycle due to the utilization of folate intermediates for DNA methylation and DNA formation [2]. Currently, many studies have been performed analyzing the effects of folic acid and folate on different organisms and for different purposes, with great focus into pathogenesis of neurodegenerative and cardiovascular disease [3]. Similarly to how DNA methylation regulates gene expression, RNA interference (RNAi) plays an important role as an epigenetic regulator for genetic and genomic expression, with current focus to use micro RNA (miRNA) as a potential vector for disease management and treatment [3]. Current studies have identified miRNA to interact with messenger RNA (mRNA) through binding and subsequent degradation, resulting in a regulated expression of proteins. Currently, 38,589 miRNAs have been identified across multiple organisms and recorded in miRBase [4][5][6][7][8][9]. After the initial discovery of miRNA regulation in C. elegans [10], the organism is actively being used in current research as an efficient and well-equipped model for studying RNAi pathways and worm development. Additionally, many miRNAs discovered have shown high conservation between homosapiens and C. elegans [11]. However, miRNAs are still not fully understood. As such, to further scientific knowledge and our understanding of RNAi pathways, studying the RNAi pathways and miRNAs involved during the development of C. elegans can provide insight into how the organism regulates the enzymes involved and the consequential effects of supplementation of vitamins on organismic health. 

1. Koseki K, Maekawa Y, Bito T, Yabuta Y, Watanabe F. High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans. Redox biology. 2020 Oct 1;37:101724. 

2. Annibal A, Tharyan RG, Schonewolff MF, Tam H, Latza C, Auler MM, Grönke S, Partridge L, Antebi A. Regulation of the one carbon folate cycle as a shared metabolic signature of longevity. Nature communications. 2021 Jun 9;12(1):1-4. 

3. Beckett EL, Veysey M, Lucock M. Folate and microRNA: bidirectional interactions. Clinica Chimica Acta. 2017 Nov 1;474:60-6. 

4. Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function. Nucleic acids research. 2019 Jan 8;47(D1):D155-62. 

5. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic acids research. 2014 Jan 1;42(D1):D68-73. 

6. Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic acids research. 2010 Oct 30;39(suppl_1):D152-7. 

7. Griffiths-Jones S, Saini HK, Van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic acids research. 2007 Nov 8;36(suppl_1):D154-8. 

8. Griffiths-Jones S, Grocock RJ, Van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic acids research. 2006 Jan 1;34(suppl_1):D140-4. 

9. Griffiths‐Jones S. The microRNA registry. Nucleic acids research. 2004 Jan 1;32(suppl_1):D109-11. 

10. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. cell. 1993 Dec 3;75(5):843-54. 

11. Ibáñez-Ventoso C, Vora M, Driscoll M. Sequence relationships among C. elegans, D. melanogaster and human microRNAs highlight the extensive conservation of microRNAs in biology. PloS one. 2008 Jul 30;3(7):e2818




Variable Expression of Extracellular miRNA during Caenorhabditis elegans Pathogenic Infection 


Abstract

Micro RNA (miRNA) has been identified as a critical component in gene regulation and has been actively studied in a transcriptional silencing. Caenorhabitis elegans has been distinguished as a powerful model for studying miRNA functionality and application due to its heavy utilization in the nematode’s epigenetic regulatory pathway [1]. Currently, extracellular miRNA has been increasingly studied as a potential biomarker for different pathogenic conditions and diseases, such as lung health [2]. These miRNA have currently been found either inside of extracellular vesicles (EVs) or existing free-floating in extracellular fluid [3]. However, evaluating extracellular miRNA responses as a result of different microbes involved with C. elegans is an active area of research. This project aims to identify the qualitative and quantitative expressions of extracellular miRNA as part of an infection-response to pathogenic microbes. 






Mutational Analysis of Uterine Cancer Variants for Therapeutic Development

In collaboration with the Amadi Group, the Brah Group, and the Salgotra Group

Abstract

Uterine cancers are noted to be extremely prevalent amongst the population, with various causes and modes of pathogenesis. In collaboration, the project aims to identify potential therapeutic approaches for uterine endometrial cancer. This project aims to characterize and identify current variants within various types of uterine cancers involving PI3K and MTORC in relation to effects on enzyme-analyte interactions to determine the biophysical changes caused by mutations and polymorphisms in effect on potential analytes for therapeutic use in uterine cancer.