β-Hairpin Antimicrobial Peptides: Class Diversity and Sequence Analysis
About
Antibiotics are failing, and bacteria are not waiting
Why I work on peptides instead.
Antibiotic resistance reaches the clinic before it reaches the literature. In the hospital laboratories where I trained, the organisms causing intensive care infections were often resistant to the drugs available to treat them. I now study antimicrobial peptides, short membrane-active sequences that kill bacteria through a mechanism conventional antibiotics do not use. My work asks which peptide scaffolds are worth developing as antibacterials, and what the sequences that work have in common.
01 — Research
Peptides, genes, and resistant organisms
Three lines of work, from clinical isolates to sequence and structure.
Antimicrobial peptide discovery and characterization
Randall Laboratory · University of Missouri–Kansas City
β-hairpin antimicrobial peptides are a compact, membrane-active scaffold, but designing new peptides on that template requires a reference for the class as a whole: which sequences belong to it, how they vary, and what they conserve. I compared β-hairpin antimicrobial peptides across diverse source organisms, using multiple sequence alignment and phylogenetic reconstruction alongside PDB, UniProt and AlphaFold to relate sequence to structure. The analysis defined the class diversity and conserved sequence features of this structural family, a reference framework for the rational design of new peptide antibiotics. Candidates are tested for potency by minimum inhibitory concentration assay, resolved for secondary structure by circular dichroism, and followed by flow cytometry and confocal imaging quantified in FIJI and CellProfiler.
Molecular genetics of disease susceptibility and drug metabolism
Tribhuvan University · Nepal
Alcohol dehydrogenase sets the rate at which ethanol is converted to acetaldehyde, and common variants of ADH1B shift that rate enough to bear on how much people drink. For my MSc I designed and ran a case–control study of ADH1B genetic polymorphism and alcohol consumption in Nepalese populations, extracting and quantifying DNA, genotyping by PCR with agarose gel electrophoresis and gel documentation, and testing association in SPSS. The study was funded by the Nepal Health Research Council and published in Fortune Journal of Health Sciences. I am also a co-investigator on a study of the distribution of genetic polymorphisms in CYP2C9, a drug-metabolizing enzyme gene whose variants inform dosing considerations in populations with type 2 diabetes.
Clinical bacteriology and antimicrobial resistance
Chitwan Medical College Teaching Hospital · Nepal
Ventilator-associated pneumonia is one of the plainest places to see antibiotic resistance as a clinical problem rather than a projection. For my BSc research I characterized the bacteriological profile of ventilator-associated pneumonia in intensive care patients at Chitwan Medical College Teaching Hospital, isolating organisms from clinical specimens, identifying them biochemically, and testing their antimicrobial susceptibility. The resistant hospital-acquired pathogens documented in that work are the reason I moved to peptides rather than to further conventional antibiotics. I was also a co-investigator on a Nepal Health Research Council study of brucellosis sero-prevalence among people involved in animal husbandry, a zoonotic exposure that links veterinary and human infectious disease risk.
02 — Publications
Peer-reviewed publications
Reverse chronological. Author lists as printed.
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Correlation Between Magnesium and HbA1C in Type 2 Diabetes Mellitus
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Association of Apolipoprotein B / Apolipoprotein A-I Ratio with Cardio Metabolic Risk Biomarkers in Type 2 Diabetes Mellitus
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Genetic Polymorphism of Alcohol Dehydrogenase 2 (ADH1B) in Association with Alcohol Consumption in Nepalese Population
03 — Teaching
Teaching and laboratory practice
Six years of biochemistry instruction and clinical laboratory work in Nepal.
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Full-time Lecturer of Biochemistry; sub in-charge, clinical laboratory services
KIST Medical College and Teaching Hospital, Nepal
I delivered the biochemistry curriculum and served as sub in-charge of clinical laboratory services.
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Part-time Lecturer
Lord Buddha College, Nepal
I delivered the clinical pathology and molecular biology curriculum for the General Medicine and Health Assistant programs.
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Part-time Lecturer
Singh Academy, Nepal
I delivered the medical biochemistry and laboratory management curriculum.
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Junior Scientific Officer
SRL (Super Religare) Diagnostics Private Limited, Nepal
I worked in diagnostic laboratory services, performing testing and interpreting results.
04 — Awards and Grants
Awards and grants
Institutional and national research funding, and one academic award.
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Chancellor research grant
University of Missouri–Kansas City, School of Graduate Studies Research Award Program
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Paul Vordtreide Award
For greatest academic achievement in first year of PhD in Molecular Biology and Biochemistry, Division of Biological and Biomedical Sciences, University of Missouri–Kansas City
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Provincial Health Research Grant
Nepal Health Research Council
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Master's thesis and research grant
Nepal Health Research Council
05 — Education
Education
Three degrees across molecular biology, clinical biochemistry, and laboratory medicine.
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Expected
PhD, Natural Sciences (Molecular Biology and Biochemistry)
University of Missouri–Kansas City, USA
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MSc, Clinical Biochemistry
Maharajgunj Medical Campus, Tribhuvan University, Nepal
Thesis: “Genetic Polymorphism of Alcohol Dehydrogenase (ADH1B) Gene in Association with Alcohol Consumption in Nepalese Populations.”
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BSc, Medical Laboratory Technology
Chitwan Medical College, Tribhuvan University, Nepal
Research: “Bacteriological Profile of Ventilator Associated Pneumonia in ICU Patients Attending Chitwan Medical College Teaching Hospital (CMCTH).”
06 — Contact
Contact
Email is the reliable route.
I am glad to hear from anyone working on antimicrobial peptides, resistance mechanisms, or the molecular genetics of drug metabolism, and from students considering this area.