Sergey Melnikov

Sergey Melnikov

Principal Investigator

I love superheroes. And I bet you do too. It’s just that my superheroes have nothing to do with Spider-Man, or Hercules, or Phoenix. My superheroes are 100% real, and nearly as underrated. My superheroes are the little invisible proteins that endow living cells with the superpower to stay alive in the absence of food, or water, or oxygen for extraordinarily long periods of time.

We humans rapidly die in the absence of food or water. Yet many microbial species can survive these hostile conditions for thousands of years. Research in my lab is focused on understanding this extraordinary ability, which we humans do not possess.

We are specifically interested in a process we term “hibernation of biological molecules”. Our work is unified by two overarching questions: how do essential enzymes of a cell are stored in starved cells correctly, and what happens when they don’t? Because molecular hibernation is ubiquitous, we move back and forth between simple and complex organisms (bacteria, fungi, mammalian tissues). Through proteomics and structural biology, we study the fate of ribosomes and other essential molecules in stressed, starved, or metabolically inactive cells. Our work provides a mechanistic understanding of cellular dormancy, thereby providing the basis for controlling this process in pathogenic bacteria or valuable biological specimens. Our past work has identified several families of proteins that are activated in response to stress or starvation to help cells preserve their most essential enzymes from undesired activity or irreparable damage.

Karla Helena-Bueno

Karla Helena-Bueno

Postdoctoral Researcher

Karla is a scientist on a mission. Studying microbes that have an extraordinary capacity to thrive in hostile conditions, Karla aims to unveil their secrets and learn how to endow biological molecules, and possibly organisms, with the ability to tolerate extreme environments.

Before joining Newcastle University, Karla completed her BSc degree in Environmental Microbiology at Michigan State University. There, working with Professor Terence Marsh, she helped identify new natural sources of antifungal compounds.

Currently, Karla is exploring the molecular biology of extremophiles and human pathogens to understand their extraordinary capacity to resist heat, cold, starvation and other growth-limiting and life-threatening environments. Her work has been supported by the NUORS Scholarship, an award given to the very best international students pursuing a program of research at Newcastle University, an EMBO Scientific Grant that she won in 2024 to pursue her collaboration with Stefan Pfeffer’s laboratory at Heidelberg, as well as other personal awards that have kindly funded her studies into the unknown of microbial stress tolerance.

Email: karla.helena-bueno@ncl.ac.uk

Lewis Chan

Lewis I. Chan

PhD Student

Lewis (also known as Lewis the Great) is a scientist aiming to uncover the mechanistic diversity by which bacterial cells protect their most metabolically expensive molecules, the ribosomes.

His work combining evolutionary studies, cryo-EM and proteomic analysis shows that ribosome hibernation factors—long thought to be highly conserved across bacteria—are in fact prone to dramatic structural divergence and frequent loss across bacterial species.

Currently, Lewis is exploring the implications of these findings to bacterial tolerance (or lack thereof) to starvation and stress. His work has been supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Doctoral Training Partnership, funding that has enabled his investigations into the evolutionary principles governing stress tolerance and adaptation in microbial life.

Email: l.i.chan1@ncl.ac.uk

Alumni

Chinenye Ekemezie

Chinenye Ekemezie

PhD Student from 2021 to 2025

Chinenye (aka Nenye) is a medical microbiologist who worked to help solve the emerging global problem of antimicrobial resistance. Her motivation was to improve global health by finding new sources of antimicrobials and new strategies to reduce the risk of resistance evolution — in short, to make drugs last longer.

Before joining Newcastle University, Chinenye completed her MSc degree in Medical Microbiology at the University of Ibadan, Nigeria. There, working with Professor Iruka Okeke, she helped characterize the antimicrobial activity of medicinal plants that have been used for centuries by African tribes as wound-healing agents. In the Melnikov Lab, Chinenye used experimental evolution as a discovery tool to find new antimicrobial drugs and better strategies for their use to combat drug-resistant pathogens. Her work was supported by the MRC Studentship.

Chinenye successfully defended her PhD thesis in 2025 and, during her time in the lab, produced multiple first- and co-first-authored publications. After defending her thesis and receiving the Doctoral College Thesis Prize Medal, she continued her scientific journey by joining Christin Dunham’s lab as a postdoctoral scientist.

Selected publications

Extensive natural variation in bacterial ribosomal drug-binding sites

Cell Reports, 2025 · Ekemezie & Chan et al. (co-first authors)

Ribosomes from certain bacteria possess divergent drug-binding sites compared to those of Escherichia coli, leading to natural evasion or hypersensitivity to antibiotics. Chinenye and co-first author Lewis Chan revealed the extent of this natural diversity across the bacterial tree of life, and built a web tool allowing researchers to compare ribosomal drug-binding residues between any species and E. coli.

Read the paper →

Hibernating ribosomes as drug targets?

Frontiers in Microbiology, 2024 · Ekemezie & Melnikov

A first-authored review exploring whether ribosomes in their dormant, hibernating state — the form in which they spend a large fraction of their time in bacterial cells — could serve as novel targets for antimicrobial drugs.

Read the paper →

Evolution of drug-binding residues in eukaryotic ribosomes

Cell Reports, 2025 · Chan & Ekemezie et al. (co-first authors)

Drugs that target eukaryotic ribosomes are becoming increasingly important as research tools and potential therapies against cancer and pathogenic eukaryotes. In this co-first-authored companion paper to their bacterial study, Chinenye and Lewis Chan traced the evolutionary history of ribosomal drug-binding sites across the eukaryotic tree of life, finding that some clades have diverged from the human ribosome more than humans have diverged from bacteria.

Read the paper →

Charlotte Brown

Charlotte Brown

PhD Student from 2021 to 2026

Charlotte is a computational scientist whose work focused on understanding how forces of evolution shape parasitic organisms. Studying microbes that have been living as parasites for millions of years, her goal was to unveil their common vulnerabilities that could serve as therapeutic targets.

Before joining the lab, Charlotte completed her MSc degree in Computational Biology at Newcastle University, UK. She then worked for the National Health Service where she helped create a pipeline for automated and rapid detection of human pathogens through DNA sequencing to enable personalized patients’ treatment. In the Melnikov Lab, Charlotte used structural biology and comparative genomics to understand the impact of the parasitic lifestyle on the molecular machines of living cells. Her work was supported by the BBSRC Studentship.

Charlotte successfully defended her PhD thesis in 2026 and, during her time in the lab, contributed to multiple co-first-authored publications spanning computational genomics, structural biology, and database development.

Selected publications

The evolutionary lifecycle of ribosome hibernation factors

bioRxiv, 2025 · Chan, Omae, Brown et al.

Analysing 46,015 complete bacterial genomes, this study reveals that ribosome hibernation factors — long assumed to be conserved across bacteria — in fact follow a dramatic evolutionary lifecycle: emerging as large ancient proteins, gradually shrinking, and going completely extinct in over 10% of studied species, only to be reinvented through gene transfers, de novo birth, or fusion with other stress-response proteins.

Read the preprint →

A conserved ribosomal protein has entirely dissimilar structures in different organisms

Molecular Biology and Evolution, 2024 · Schierholz, Brown & Helena-Bueno et al. (co-first authors)

Co-first-authored structural biology study revealing that a supposedly conserved ribosomal protein adopts dramatically different three-dimensional structures across organisms — a striking example of how evolution can radically reshape a molecule’s architecture while preserving its function.

Read the paper →

Ribosomal proteins can hold a more accurate record of bacterial thermal adaptation compared to rRNA

Nucleic Acids Research, 2023 · van den Elzen, Helena-Bueno, Brown et al.

Contributing author on this study showing that ribosomal proteins carry more reliable molecular signatures of an organism’s preferred growth temperature than ribosomal RNA — with broad implications for predicting thermal adaptation from genome sequences.

Read the paper →