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grant:DN13/14/20.12.2017, Design and experimental validation of chimeric antisense oligonucleotides as antibacterial agents awarded by the Bulgarian National Science Fund (BNSF), featured on the website of Sofia University (see the image below)

grant:DN13/14/20.12.2017

Goal: The main goal of this project is to continue a very successful research in the field of RNA synthetic and computational biology, medicine and pharmaceutical started by the project leader Dr. rer. nat. Robert Penchovsky several years ago as a postdoctoral fellow at Yale University. His main background research is based on computer engineering of oligonucleotides. Our idea for this Project is to design antisense oligonucleotides, which are directly binding and regulating the target bacterial pathogen’s riboswitches. The riboswitches are structured RNA domains usually residing at the 5’-untranslated region of messenger RNAs that directly bind specific metabolites. They serve as logic gates regulating gene expression. As a result, riboswitches enable mRNAs to regulate their own expression without the need of any regulatory proteins. This way, the essential metabolites for the bacteria will not be synthesized by the cell or transported into the cell from the extracellular matrix. The result is the death of Staphylococcus aureus for instance. Antisense oligonucleotides show bacteriostatic effect and can be tested as novel antibacterial agents in bacterial isolates and human embryonic kidney cell lines (HEK 293) for toxicity.

You can see a presentation of the results of the project DN13/14/20.12.2017 (in Bulgarian only) for the first-half of the project. The video is also available on YouTube.

The research of the project is published in 20 publications (with an impact factor of 84 points and Q1-4 of 274 points - see below, and 86 citations so far), participation in 3 conferences with 2 presentations and 4 posters, made 16 pieces of software, 4 Ph.D. and 1 master students - all graduated with me as a supervisor. This research grant is funded by 61000 EUR only.

More links on the grant's results:1. Bulgarian National Science Fund, 2. Bulgarian Ministry of Education and Science, 3. Magazine of Bulgarian Science, 4. Robert's interview for the Bulgarian National Radio(BNR) broadcasted on March 24, 2022, and 5.Robert's interview for Science_BG: video, given in Bulgarian on March 2, 2022, 6.Robert's interview for Science_BG: podcast, given in Bulgarian, broadcasted on April 21, 2022

Our doctoral student Georgi Miloshev won the prize doctoral student of the year 2022 of Sofia University! Georgi works on several research projects, including DN13/14/20.12.2017, KP-06-H31/18/13.12.2019, and KP-06-M33/5/18.12.2019 awarded by the BNSF (for more information click here).

Publications for the first-half of the project:

1. Nikolet Pavlova, Dimitrios Kaloudas & Robert Penchovsky, Riboswitch distribution, structure, and function in bacteria, Gene, 8, 38-48 (2019), IF: 2.5, (Q1, Scopus)

2. Nikolet Pavlova & Robert Penchovsky, Genome-wide bioinformatics analysis of FMN, SAM-I, glmS, TPP, lysine, purine, cobalamin, and SAH riboswitches for their applications as allosteric antibacterial drug targets in human pathogenic bacteria, Expert Opinion on Therapeutic Targets, 23, 631-643, (2019), IF: 4.5, (Q1, Scopus)

3. Nikolet Pavlova, Dimitrios Kaloudas & Robert Penchovsky, EBWS: Essential Bioinformatics Web Services for Sequence Analyses, IEEE Transactions on Computational Biology and Bioinformatics, 16, 942-953 (2019), IF: 2.4, (Q1, Web of Science)

4. Robert Penchovsky, Automated DNA hybridization transfer with movable super-paramagnetic microbeads in a microflow reactor, Biosensors and Bioelectronics, 135, 30-35, (2019), IF: 8.2, (Q1, Scopus)

5. Katya B Popova, Lozena A Otcheva, Martina Traykovska & Robert Penchovsky, RNA as a Potent Target for Antibacterial Drug Discovery, Biomedical Journal of Scientific and Technological Research, 16, 942-953 (2019), IF: 0.7

6. Martina Traykovska, Sjoerd Miedema & Robert Penchovsky, Clinical Trials of Functional Nucleic Acids: Antisense Oligonucleotides and Aptamers, International Journal of Biomedical and Clinical Engineering, 7, 1-15 (2018), IF: 0.5

7. Robert Penchovsky and Aikaterini Valsamatzi-Panagiotou, Engineering antisense oligonucleotides as antibacterial agents, Arch Clin Microbiol, (2019), IF: 0.16, (Q4, Scopus)

8. Robert Penchovsky, Nikolet Pavlova and Dimitrios Kaloudas, ExBWS: Extended Bioinformatics Web Services for Sequence Analyses, International Journal of Bioinformatics Research and Applications, (2021), IF; 0.85, (Q4, Scopus)

9. Aikaterini Valsamatzi-Panagiotou, Martina Traykovska, & Robert Penchovsky, Mechanisms of Drug resistance and Approaches to overcome it, Elsevier (2020)

Publications for the second-half of the project:

10. Lozena A Otcheva, Nikolet Pavlova, Katya B Popova, Martina Traykovska and Robert Penchovsky, Why Some Riboswitches are Suitable Targets for Antibacterial Drug Discovery? - EC Microbiology (2020)…IF:1.73

11. Katya B Popova and Robert Penchovsky, Why Some Functional RNAs Such as Bacterial Riboswitches are Versatile Targets for Antibacterial Drug Discovery? - EC Microbiology (2020)…IF:1.73

12. Martina Traykovska, Katya B. Popova and Robert Penchovsky, Targeting glmS ribozyme with chimeric antisense oligonucleotides for antibacterial drug development, ACS Synthetic Biology… (2021), IF:5.5 (Q1, Scopus)

13. Aikaterini Valsamatzi-Panagiotou, Katya B. Popova, Robert Penchovsky, Sustainable Agriculture Reviews 49 Mitigation of Antimicrobial Resistance Vol. 2, Natural and Synthetic Approaches, Chapter 1: Strategies for prevention and containment of antimicrobial resistance(2021) Springer…

14. Katya B Popova and Robert Penchovsky, Current Activators of the glmS Riboswitch - Biomedical Journal of Scientific and Technological Research (2021)…IF:0.548

15. Katya B. Popova, Aikaterini Valsamatzi-Panagiotou and Robert Penchovsky New drug discovery strategies for targeting drug - resistant bacteria - Environmental Chemistry Letters (2021)…IF:13, (Q1, Scopus)

16. Aikaterini Valsamatzi-Panagiotou, Katya B. Popova, Robert Penchovsky,Methods for prevention and constraint of antimicrobial resistance: a review - Environmental Chemistry Letters (2021)…IF:13, (Q1, Scopus)

17. Dimitrios Kaloudas, Nikolet Pavlova and Robert Penchovsky, Phycoremediation of wastewater by microalgae: a review - Environmental Chemistry Letters (2021)…IF:13, (Q1, Scopus)

18. Dimitrios Kaloudas, Nikolet Pavlova and Robert Penchovsky, Lignocellulose, algal biomass, biofuels and biohydrogen: a review - Environmental Chemistry Letters (2021)…IF:13, (Q1, Scopus)

19. Robert Penchovsky, Nikolet Pavlova and Dimitrios Kaloudas, RSwitch: a novel bioinformatics database on riboswitches as antibacterial drug targets - IEEE Transactions on Computational Biology and Bioinformatics (2020)…IF:2.8, (Q1, Web of Science)

20. Aikaterini Valsamatzi-Panagiotou, Katya B. Popova, Robert Penchovsky, Sustainable Agriculture Reviews 46, Mitigation of Antimicrobial Resistance Vol. 1, Tools and Targets: Chapter 9: Drug Discovery for Targeting Drug Resistant Bacteria (2020) Springer…

Conferences for the first-half of the project:

1. 19th EuroSciCon Conference on Microbiology and Virology, invited lecture on "Engineering antisense oligonucleotides as antibacterial agents" April 22-23, 2019 in Athens, Greece, with one talk.

2. 14th Congress of Microbiologists in Bulgaria with International Participation invited lecture on "Design and application of antisense oligonucleotides as antibacterial agents" October 10-13, 2018 in Hisarya, Bulgaria, with one talk and three posters, including an award wining poster.

3. German Conference on Bioinformatics, September 25-28, Vienna, Austria 2018, with one poster.

Software produced within the first half of the project:

1. RevComOligo: If you want to have your reverse complementary DNA sequence click here…

2. RandomOligoGenerator: If you want to have random DNA, RNA or peptide sequences click here…

3. Motif Searcher: If you want to search for motifs in any DNA, RNA or peptide sequences click here…

4. Restriction Mapping: If you want to search for restriction sites in DNA sequences click here…

5. Prokaryotic ORF Finder: If you want to search for Open Reading Frames (ORFs) in prokaryotic DNA sequences click here…

6. DNA/RNA Mutations: If you want to perform random DNA or RNA mutations at different rates click here…

7. DNA/RNA TM Calculator: If you want to calculate the melting temperature (TM) of DNA or RNA click here…

8. Guide RNA Generator: If you want to generate guide RNA sequences for CRISPR/Cas9 system click here…

9. PCR Annealing Temperature Calculator: If you want to calculate the annealing temperature for PCR reaction click here…

Software produced within the second-half of the project:

10. DNA/RNA Translator: If you want to translate DNA or RNA sequence click here…

11. RandomOligoGenerator: If you want to change a protein sequence from one letter code to three letters and vice versa click here…

12. Virtual PCR: If you want to perform a PCR reaction click here…

13. HydropathyPlot-Proteins: If you want to perform a Hydropathy plot of an amino acid sequence click here…

14. Reverse Translator: If you want to perform a Reverse translation of a protein sequence click here…

15. Eukaryotic ORF finder: If you want to search for Open Reading Frames (ORFs) in Eukaryotic DNA sequences click here…

16. RSwitch database: To browse the RSwitch database of riboswitches as antibacterial drug targets click here…

Graduated Doctoral Student within the first half of the project:

1. Dr. Nikolet Pavlova works on the project. She has graduated her doctoral study on October 16th, 2019.

Graduated Doctoral Student within the second-half of the project:

2. Dr. Lozena Otcheva from Bulgaria, a former Doctoral student. Lozena holds Master's degree in Pharmacy and Industrial Pharmacy from the University  of Rome, Italy. She has graduated her doctoral study on February 10th, 2021.

3. Dr. Katya Popova, from Bulgaria, a former Doctoral student. Katya holds a Bachelor's degree in Biology and a Master's degree in Genetics and Genomics from Sofia University, Bulgaria. She has graduated her doctoral study on April 16th, 2021.

4. Dr. Aikaterini Valsamatzi, from Greece, a former Doctoral student. Aikaterini holds a Master's degree in Medicine from Medical University-Plovdiv, Bulgaria. She has graduated her doctoral study on April 14th, 2021.

Graduated Master Student within the first-half of the project:

1. One master student graduated while working on the project (see the table from number 17).