Research profile and actual research tasks:
Research Profile:
- Molecular Structure of Bacteriophage Virions
- Identification of structural proteins of bacteriophages, analysis of their biological functions, structural analysis.
- Utilization of capsid proteins as molecular targets for modifying the biological properties of the phage capsid.
- Immunogenicity of bacteriophage proteins: identification of epitopes, analysis of antibody formation, deimmunization of phages through engineering of the structural proteins that make up virions.
2. Pharmacokinetics of Bacteriophages
- The role of the immune system in humans and animals and the response to individual phage proteins in shaping the bioavailability of bacteriophages in vivo.
- Interactions and balance between the microbiome, “phageome,” and the human organism, with particular emphasis on active proteins and amino acid motifs.
3. Phage Enzymes
- Identification of new bactericidal enzymes of phage origin.
- Characterization and engineering of phage enzymes, interactions with the immune system in humans and animals.
Currently Ongoing Research Tasks (within statutory activities):
- Analysis of biologically active bacteriophage proteins in model phages and/or viromes of human and animal origin. This task is a continuation of ongoing research on the molecular basis of bacteriophage biological activity.
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- Aim: Identification of reactive phage proteins in selected model bacteriophages and/or in human and animal viromes; determination of the biological functions of these proteins and their molecular elements that mediate interactions between phage virions and host organisms; characterization of phage protein-mediated interactions.
- Expected scientific and practical outcomes: Discovery of previously uncharacterized interactions between bacteriophages and human or animal organisms and the mechanisms underlying these interactions. Identification of molecular targets suitable for engineering to enable controlled modulation of phage-host interactions. Potential to modify bacteriophage biological activity for therapeutic or prophylactic applications, and to advance our understanding of phage roles as components of the human and animal virome.
- Validation of phage display-based serological profiling as a method to assess hypersensitivity to selected allergens. This task continues previous work on phage display-based epitope libraries for antibody specificity profiling.
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- Aim: Adaptation of previously developed high-throughput IgG serological profiling methods to the detection and analysis of IgE antibodies; optimization and validation of methodology.
- Expected scientific and practical outcomes: Development of a robust, high-throughput platform for identifying IgE antibodies recognizing various allergens in human populations and in murine hypersensitivity models. This includes designing and constructing phage display epitope libraries based on in silico predictions, followed by library testing and analysis. The reactivity of individual library components will be assessed via NGS-based sequencing. The project is expected to result in an innovative method for simultaneous detection of thousands of allergens relevant to diverse research contexts.
Currently Ongoing Research Tasks (within grant activities):
- Identification of bacteriophage epitopes significant for human health (prof. dr hab. Krystyna Dąbrowska NCN OPUS 18, 2019/35/B/NZ7/01824).
- The goal of the project is to identify reactive epitopes present in the structural proteins of bacteriophages and then to assess the level of specific immunization at the population level, including groups of individuals exhibiting certain health disorders.
- Combining bacteriophages and other antibacterial agents as a strategy to combat multidrug-resistant E. coli and K. pneumoniae (prof. dr hab. Krystyna Dąbrowska NCN/UE JPIAMR ACTION Call 2024, UMO-2024/06/Y/NZ7/00178).
- The aim of the project is generating pivotal information on how to optimally combine phages and antimicrobials by using several infection models – in silico, in vitro, ex vivo, cell culture, patient-derived organoid models, and murine animal models. We will also investigate the emergence of phage resistance and development of antibodies in animals receiving long-term treatment with phages. This project explores the utility of phage-antimicrobial combinations in various infection models and will direct roadmaps for clinical use.
- Mechanisms of interactions between bacteriophage-derived ‘dark matter’ and the mammalian immune system (prof. dr hab. Krystyna Dąbrowska, NCN-NSFC (China) Sheng2 UMO-2021/40/Q/NZ7/00202).
- Bacteriophages (phages) are viruses that can kill bacteria, including those bacteria that infect and endanger humans. We know phage biology, however exact functions of phage genes have not been discovered yet in many cases. These genes are so-called “phage dark matter” and they probably mediate many important functions of phage. These functions are often difficult to identify since they are not self-evident: they may relate to how phage interacts with animal and human organisms, even though phage is a bacterial virus, not able to infect animal or humans. However, not able to infect does not necessary mean not able to interact with. The goal of this project is to find out how and why our immune system responds to proteins produced by bacteriophages, with special regard to the proteins that belong to the phage-derived dark matter.
- Bactericidal properties of a bacteriophage-derived protein active against Staphylococcus aureus, including drug-resistant strains (prof. dr hab. Krystyna Dąbrowska, NCN Opus-26 Grant UMO-2023/51/B/NZ7/00799).
- Recurrent Respiratory Papillomatosis (RRP) is a rare and perplexing condition that can affect anyone, from kids to adults, irrespective of gender. The defining feature of this ailment is the appearance of wart-like growths on the respiratory lining and the beginning of the digestive tract. These growths, akin to warts, are caused by an infection from the human papillomavirus (HPV), a notorious virus known for causing various infections in the skin, respiratory system, and genital areas of both men and women. Just to give you a sense of the diversity, scientists have identified over 200 types of HPV so far, and in the case of RRP, it’s primarily the HPV6 and HPV11 types responsible for 83-100% of cases. Despite HPV being pretty common, with many folks carrying it around without issues, why does the virus decide to set up shop and cause symptoms in only some people? Surprisingly, there’s not much out there in terms of research discussing the trio of gut microbiota, immunology, mucosa, and HPV infection. By the end of our project, we’re hoping to uncover how the immune system, infection course, and gut microbiota dance together in patients dealing with recurrent respiratory papillomatosis. Who knows, maybe our findings will be a piece of the puzzle in understanding this complex relationship.
- Bactericidal properties of a bacteriophage-derived protein active against Staphylococcus aureus, including drug-resistant strains (dr Zuzanna Kaźmierczak NCN SONATA 19, 2023/51/D/NZ7/02145).
- This project investigates the phage-derived protein orf096 as a novel antibacterial agent against Staphylococcus aureus, including drug-resistant MRSA strains. The study will characterize its molecular mechanisms of action, and evaluate its stability as a potential therapeutic. By developing alternatives to conventional antibiotics, this research addresses the urgent global challenge of antimicrobial resistance in a major human pathogen responsible for serious clinical infections.
- The role of a novel antibacterial agent targeting the bacterial community in respiratory diseases and identification of key factors shaping its antibacterial activity (dr Paulina Miernikiewicz NCN SONATA 19, 2023/51/D/NZ6/02589).
- The aim of the project is to investigate a phage-derived lysin specific to Rothia spp., which may reduce the severity and persistence of Pseudomonas aeruginosa lung infections by inhibiting its metabolism and creating an unfavorable environmental niche. The study focuses on the bacteriolytic activity of this lysin against Rothia mucilaginosa and Pseudomonas aeruginosa, both of which are associated with severe and chronic respiratory diseases.
- Profiling of the phageome in relation to clinical outcomes in patients undergoing radical cystectomy and urinary diversion using a segment of the gastrointestinal tract (dr inż. Katarzyna Gembara, NCN SONATINA 52, DEC-2024/52/C/NZ6/00335 podmiot realizujący: Wojewódzki Szpital Specjalistyczny we Wrocławiu)
- The aim of the project is to investigate the transformation of the intestinal phageome into the urinary tract phageome following radical cystectomy in bladder cancer patients, and to determine its impact on the bacterial microbiome and clinical outcomes. This will be achieved through microbiome profiling of resected bladders, intestinal segments used for urinary diversion, and urine samples collected before and after surgery. By combining Next Generation Sequencing with comprehensive bioinformatic and statistical analyses, the project will explore how intestinal tissues adapt to their new urinary function and how this affects microbial communities, particularly bacteriophages. The project introduces a novel perspective by focusing on the phageome changes during tissue repurposing and aims to uncover their potential role in postoperative complications, especially urinary tract infections. These findings will support the development of microbiome-informed strategies for improving surgical outcomes and patient care after radical cystectomy.
Head: Prof. Krystyna Dąbrowska, PhD, DSc (0000-0002-1518-3183)
Molecular biologist; current field of research: studies on immune response to bacteriophages as it relates to phage therapy trials; phage pharmacokinetics and the effects of phages on mammalian systems and cells, including safety aspects; molecular determinants of innate and adaptive immune responses to the microbiome, with a special focus on the phageome.
Main methodological expertise: gene cloning, recombinant proteins and protein science, directed mutagenesis, transcriptomics, real-time PCR, cell cultures, animal models, antibodies, phagocytes, cytokines, tumor models, phage display, clinical microbiology, bioinformatics.
Education and scientific degrees
21.07.2020 Professor of Natural Sciences, conferred by the President of the Republic of Poland upon the recommendation of the Central Commission for Academic Degrees and Titles; Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
2004 – 2015 D.Sc. (Polish: dr hab.) in Biological Sciences, Medical Microbiology; Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. Thesis title: “Studies of structural bacteriophage proteins with the aim of phage therapy development: identification of biological properties and development of new technological solutions in the T4 phage model.” (5 Mar 2015)
2000 – 2004 Ph.D. in Biological Sciences, Biology; Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. Thesis title: “Studies of phage-mammalian cells interactions and potential impact of these interactions.”
1998 – 2000 M.Sc. in Biological Sciences, Genetics; Wrocław University, Dept. of Natural Sciences. Thesis title: “Functional and structural analysis of the gene YPR117w in Saccharomyces cerevisiae.”
1995 – 1998 B.Sc. in Biological Sciences, Environmental Protection and Ecology; Wrocław University, Dept. of Natural Sciences
Additional education (12 most important selected):
2011 Postgraduate diploma in ‘Project management’, Faculty of Management, Information Systems and Finance, Wrocław University of Economics (1 academic year)
2012 ‘Enterprisers’ training, Centre for Entrepreneurial Learning, University of Cambridge (5 days)
2013/2014 Foundation for Polish Science, SKILLS series: ‘Scientific team leading’, ‘Scientific writing’, ‘Managing Scientific Teams’, ‘Negotiations for Scientists’, Presentation Skills and Public Speaking’ (2 days each)
2015: ‘Annotation Workshop’ on bioinformatic analysis of bacteriophage genomes, led by Prof. A. Kropinski, University of Guelph, Canada (5 days)
2016: ‘Genome Technology Course’, trainer: Prof. R. Lavigne, Katholieke University Leuven, Belgium, Wrocław University (5 days)
2018: ‘Ion Torrent AmpliSeq and Bioinformatics Individual Training’, 20-hour practical training in wet lab and bioinformatic analysis of next-generation sequencing data, ThermoFisher Scientific.
2021: ‘Effective Public Speaking’, Radio Wrocław Training Center, Wrocław (1 day)
2022/2023: Optima Center for Development and Staff Training, Management Certificate series (online): ‘Team Leader Public Speaking’ training’, ‘Effective Time Management’, ‘Self-Management in Crisis Situations’, ‘Managing Emotions and Strengthening Psychological Resilience of Leaders’, ‘Ethical Influence and Defense Against Manipulation in Professional Situations’ (1 day each)
2022/2023: Data2biology sp. z o.o., Poznań, Bioinformatics series (online). ‘Python for Biologists’ – Parts 1 and 2, ‘Analysis and Visualization of Biological Data in R’, ‘Introduction to RNA-Seq Data Analysis’, ‘RNA-Seq Data Analysis in R’ – Parts 1 and 2, ‘single cell RNA sequencing analysis in R’ (2 days each)
2023: StatSoft Polska Sp. z o.o, Statistics in Medicine series (online) – ‘Basic Methods’, ‘Analysis of Qualitative Data’, ‘Introduction to Power Analysis and Sample Size Estimation’, ‘Methods of Variance Analysis and Regression Analysis’ (2 days each)
2023: New Opportunities program, Your New Possibilities Association, Wrocław: ‘Awareness Training on Recognizing the Needs of People with Disabilities and Specific Health Needs’, and ‘Awareness Training on Recognizing the Needs of People in Mental Health Crisis’ (1 day each)
2024: ‘Introduction to AI Programming in Python’, Xenstats Poznań (online) (2 days)
Employment
04.09.2023 – to date Professor, Wrocław Institute of Science and Technology, Wrocław, Poland.
01.08.2021 – to date Head of Phage Molecular Biology Lab, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
01.11.2020 – to date Professor, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
01.09.2017 – to date Head of Genetic Engineering Department, Research and Development Centre, Regional Specialist Hospital Wrocław, Poland
20.01.2016 – to date Head for Science, Research and Development Centre, Regional Specialist Hospital Wrocław, Poland
18.06.2015 – 30.10.2020 Associate professor, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
01.07.2005 – 17.06.2015 Assistant Professor, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
01.01.2005 – 01.07.2005 laboratory assistant, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
16.11.2004 – 01.01.2005 laboratory technician, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
15.11.2000 – 15.11.2004 PhD student, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Foreign trainings (selected)
2013 24.10.2011-04.11.2011
Division of Gene Technology, Katholieke Universiteit Leuven, Leuven, Belgium, Prof. Rob Lavigne, title of joint research project: Gene cloning, protein expression, and antigenicity studies in structural proteins of Pseudomonas F8-related phages. Continued collaboration in a joint research grant from the National Science Centre.
04.08.2012-08.08.2012, 03.04.2013-08.04.2013, 23.04.2014-30.04.2014, 22-29.06.2014
University of Texas Medical School, Houston, USA, Prof. Emil Martin. Visits within the 2-year program of the Foundation for Polish Science ‘SKILLS – Mentoring’, visit purpose: substantive training: “Cell signaling, theory, and practice”, scientific collaboration.
15.09.2013-19.09.2013, 14-19.06.2019
University of Minho, Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Braga, Portugal, Prof. Joana Azeredo, project topic: Investigation of the immunological properties of Pseudomonas bacteriophages (2013);
Scientific visit within the Erasmus+ program, visit topic: “Immunogenicity of Pseudomonas phages” (2019).
21.04-04.05.2017
University of Maryland, Institute for Bioscience and Biotechnology Research, Laboratory of Antimicrobial Discovery, Rockville, USA, Prof. Daniel Nelson, project topic: Diversity of the immunological reactivity of endolysins as a determinant of differences in their antibacterial efficacy in vivo.
8-11.11.2022
UIT The Arctic University of Norway, IMB Vascular Biology (Norwegian Arctic University, Institute of Vascular Biology), Tromsø, Norway, Prof. Karen Kristine Sørensen, project topic: identification of structural proteins determining the pharmacokinetics of bacteriophages.
Awards and scholarships (10 most important selected)
2005 UNESCO and L’Oréal For Women in Science Award, one-year individual fellowship, category: PhD students, Polish edition
2007 Foundation for Polish Science ‘Start Award’, the major award for young scientists in Poland, one-year individual fellowship
2007 National Geographic Traveler 2007 Scientific Discovery of the Year ‘Bacteriophage therapy’, team award for IIET Bacteriophage Laboratory
2011 Foundation for Polish Science ‘Conference Award’ for the conference presentation ‘Molecular imaging of Hs294T melanoma homing in athymic NCr nu/nu mice lungs and the stimulatory effect of LPS’ at the American Association for Cancer Research 102nd Annual Meeting, Innovation and Collaboration: the Path to Progress, Orlando, USA, 02-06.04.2011
2015 Commendation for the second thesis (D.Sc. degree), Scientific Board of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
2016: ‘Lecturer of the Year 2015/2016’ Award, University of Children Foundation, awarded by UD students, 24.09.2016
2017: Distinction in the national competition named after Prof. K. Bassalik for the best Polish microbiological works published in 2015 for the publication: Hodyra-Stefaniak K., Miernikiewicz P., Drapała J., Drab M., Jończyk-Matysiak E., Lecion D., Kaźmierczak Z., Beta W., Majewska J., Harhala M., Bubak B., Kłopot A., Górski A., Dąbrowska K. (2015). Mammalian Host-Versus-Phage immune response determines phage fate in vivo. Sci Rep. 5:14802, 20.03.2017
2017: Director’s Award of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, for outstanding achievements in scientific and organizational activities for the years 2014-2016, 02.06.2017.
2018: Director’s Award of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, for publishing the original work with the highest impact factor in the category ‘leading role of IITD PAN’, 11.10.2018
2022: Team Director’s Award of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, for publishing the original work with the highest impact factor (IF) in the category ‘leading role of IITD PAN’, 20.10.2022, regarding the publication: Kaźmierczak Z., (et al.), Dąbrowska K. Immune Response to Therapeutic Staphylococcal Bacteriophages in Mammals: Kinetics of Induction, Immunogenic Structural Proteins, Natural and Induced Antibodies. Frontiers in Immunology 12:639570, 2021.
2025-2026: Fulbright Senior Award for a middle-term stay in Stanford Medical Schood, US
Principal Investigator in research grants (NCN- national Science Centre in Poland)
NCN Sheng2 Grant, registration no. UMO-2021/40/Q/NZ7/00202, funding amount: 448,404.00 EUR, implementation: 15.12.2021-14.12.2025, title: “Mechanisms of ‘dark matter’ of bacteriophage origin interactions with the mammalian immune system”,
NCN Opus-18 Grant, registration no. UMO-2019/35/B/NZ7/01824, funding amount: 519,552.00 EUR, implementation: 25.06.2020 – 24.06.2025, title: “PhageScan: Identification of bacteriophage epitopes of significance to human health”,
NCN Opus-15 Grant, registration no. UMO-2018/29/B/NZ6/01659, funding amount: 385,308.00 EUR, implementation: 24.01.2019 – 23.01.2022, title: “Gastric microbiome of Helicobacter pylori-infected individuals”,
NCN Harmonia 7 Grant, UMO-2015/18/M/NZ6/00412, funding amount: 243,936.00 EUR, implementation: 12.04.2016 – 11.03.2020, title: “Diversity of immune reactivity of endolysins as a determinant of their antibacterial efficacy in vivo”,
“Mozart” Grant of the Municipal Program of Support for Higher Education and Science Partnership with the Economic Activity Sector, Wrocław City Hall BWU-2/2015/M4, funding amount: 8,448.00 EUR, implementation: 01.10.2015-30.09.2016,
NCN Harmonia Grant, UMO-2013/08/M/NZ6/01022, funding amount: 109,230.00 EUR, implementation: 17.09.2013 – 16.06.2016, title: “Identification of molecular features determining the immunogenicity of PB1 group bacteriophages active against Pseudomonas”,
NCN Sonata bis Grant, UMO-2012/05/E/NZ6/03314, funding amount: 317,900.00 EUR, implementation: 14.02.2013 – 14.08.2017, title: “Identification of the impact of bacteriophages with therapeutic potential on cellular functions and the mammalian immune system”,
NCN/KBN Grant, N N401 147539, funding amount: 83,600.00 EUR, implementation: 06.09.2010-31.03.2014, title: “Study and design of the influence of T4 family bacteriophages on cancer and immune processes at the molecular level: modifications of active capsid motifs”,
NCN/KBN Grant, 2P05B 078 28, funding amount: 39,600.00 EUR, implementation: 09.05.2005-08.05.2007, title: “Study of interactions with cancer cells and comparison of T4 and HAP1 bacteriophage activity”,
Young Scientist Grant by KBN, 6P05A 076 21, funding amount: 4,400.00 EUR, implementation: 01.10.2001-01.10.2002, title: “T4 bacteriophage – selection and characterization of mutants with prolonged persistence in BALB/c mice”
Scientific Supervisor of PhD grants (NCN- national Science Centre in Poland)
NCN Preludium Grant, number: UMO-2019/35/N/NZ6/02564, funding amount: 30,800.00 EUR, implementation: 25.06.2020-24.06.2022, title: “Enhancing the therapeutic potential of proteins through specific, planned modifications using bacteriolytic lysins as an example.”, Scientific Supervisor (PI: PhD student, Marek Harhala).
NCN Preludium Grant, UMO-2018/31/N/NZ6/02584, funding amount: 46,200.00 EUR, implementation: 01.07.2019 – 30.06.2022, title: “Translocation of bacteriophages as components of the gut microbiome”, Scientific Supervisor (PI: PhD student, Aleksander Szymczak).
NCN Preludium Grant, UMO-2017/25/N/NZ6/02372, funding amount: 26,400.00 EUR, implementation: 15.02.2018 – 30.06.2021, title: “Gastrointestinal environment as a source of selective pressure directing the evolution of T4 bacteriophage capsid”, Scientific Supervisor (PI: PhD student, Joanna Majewska).
NCN Preludium Grant, UMO-2015/19/N/NZ4/03609, funding amount: 33,000.00 EUR, implementation: 15.06.2016-14.06.2019, title: “Study of pharmacokinetics of bacteriophages in an animal model using a new tool – fluorescently labeled bacteriophage”, Scientific Supervisor (PI: PhD student, Zuzanna Kaźmierczak).
Supervision of PhD projects
Katarzyna Hodyra-Stefaniak (PhD degree awarded in 2017), Zuzanna Kaźmierczak (PhD degree awarded in 2018), Paulina Miernikiewicz (PhD degree awarded in 2018), Marek Harhala (PhD degree awarded in 2022), Katarzyna Gembara (PhD degree awarded in 2023), Aleksander Szymczak (PhD degree awarded in 2023), Alina Szewczyk-Dąbrowska (PhD degree awarded in 2023), Joanna Majewska (PhD degree awarded in 2023), Izabela Rybicka (project in progress), Kostiantyn Rokush (project in progress), Tomasz Klimek (project in progress)
Supervision of MSC projects: 21 students in the years 2004-2020
Other
- Co-chair of the Organizing Committee (together with Prof. Zuzanna Drulis-Kawa, PhD, University of Wrocław) and Chair of the Scientific Committee of the international conference under the patronage of the European Molecular Biology Organization (EMBO) and the International Society for Viruses of Microorganisms (ISVM) 5th EMBO Workshop Viruses of Microbes 2018, July 9-13, 2018, Wrocław (http://meetings.embo.org/event/18-virus-microbe).
- Teacher at the workshop ‘To see what is not possible to see, or invisible biology’, school children workshops as part of the Lower Silesian Science Festival, (annually since 2007).
- Lectures for the HIIET Doctoral School students: ‘Immunology’, ‘Writing Publications and Grants’ (annually since 2012)
- Member of the Board and Founding Member of the Polish Society for Research on Microorganism Viruses (since July 2023)