Brandis lab

Popular science presentation

Understanding how microbes adapt, survive, and shape our world

Microorganisms may be invisible to the naked eye, but they shape our planet in profound ways. They drive global nutrient cycles, respond rapidly to environmental change, and have a major impact on human health. Our research group is driven by curiosity about how these organisms function and evolve, and by what their successes and failures can teach us about life under pressure. Our work spans molecular biology, genetics, and evolutionary biology in bacteria and yeasts. We study how microbes adapt to challenging environments, how they evolve resistance to antibiotics, and how essential cellular processes such as protein synthesis are built to be both efficient and robust. By combining evolutionary and mechanistic perspectives, we aim to understand not just what changes during adaptation, but why particular solutions emerge.

Climate change provides a striking example of evolution in action. As global temperatures rise, environmental microorganisms must rapidly adapt or disappear. We recreate this challenge in the laboratory by evolving hundreds of naturally occurring bacterial and yeast strains under gradually increasing heat stress. By combining experimental evolution with genome sequencing, we can watch adaptation unfold, uncovering both common strategies shared across species and unique solutions shaped by each organism’s evolutionary history.

Another major focus of our research is the ongoing arms race between antibiotics and bacteria. Antibiotic resistance is a growing global threat, driven by the remarkable evolutionary capacity of microbes. We study how bacteria navigate the landscape of resistance mutations and whether carefully designed antibiotic combinations can steer evolution in more favorable directions. By mapping resistance trajectories in clinically relevant strains, our goal is to generate knowledge that supports more sustainable treatment strategies.

At a more mechanistic level, we investigate the ribosome - the molecular machine that synthesizes proteins - and the processes that assemble and regulate it. Ribosome biogenesis is surprisingly flexible: many of the proteins involved are highly conserved across bacteria, yet removing them one by one often has little effect. We test the idea that ribosomes can be built through multiple alternative routes with hidden redundancies that contribute to cellular robustness. This work provides fundamental insight into how essential biological systems tolerate perturbation.

Finally, we extend this microbial perspective to human biology. Mutations in the human translational machinery are linked to genetic disorders, yet are difficult to study directly at large scale. To overcome this limitation, we are developing microbial model systems in which components of human ribosomes are engineered into single-celled organisms using modern gene-editing tools. This approach combines the experimental power of microbial genetics with the biomedical relevance of human translation.

Across all our projects, we integrate high-throughput genetic engineering, experimental evolution, genomics, bioinformatics, and molecular biology. By studying natural isolates alongside laboratory strains, we aim to capture the true diversity of life and uncover general principles that govern adaptation, robustness, and evolution in a changing world.

Research projects

Our research projects are rooted in expertise in microbial genetics, complex strain construction, and experimental evolution. By combining these approaches, we address fundamental and applied questions at the intersection of evolution, translation, and human health. Below are four examples of our central research directions.

Adaptation to rising temperatures

Global temperatures are increasing, forcing environmental microorganisms to either adapt to higher thermal stress or face extinction. How do microbes adapt to elevated temperatures? Are there shared adaptive mechanisms across the microbial tree of life, or does each species evolve unique solutions? To address these questions, we have isolated hundreds of natural bacterial and yeast strains. Using experimental evolution under gradually increasing temperature stress combined with whole-genome sequencing, we map the genetic basis of thermal adaptation. This approach allows us to distinguish strain-specific solutions from common adaptive strategies across diverse taxa.

Evolutionary dynamics of antimicrobial resistance

Antimicrobial-resistant infections represent a major global health challenge, highlighting the urgent need to optimize treatment strategies that limit the emergence and spread of resistance. In recent work, we investigated the potential of collateral sensitivity, an evolutionary trade-off in which resistance to one antibiotic increases susceptibility to another, as a tool to constrain resistance evolution (Chauhan et al., 2024). Our results indicate that while collateral sensitivity can be effective, its applicability is limited to specific species and antibiotic combinations. Building on this work, we are now developing a novel experimental platform to systematically map antibiotic resistance trajectories in clinical isolates, with a particular focus on combination therapies. The long-term goal is to generate data that can inform optimized treatment guidelines and reduce the risk of resistance development.

Robustness and redundancy in bacterial ribosome biogenesis

Bacterial ribosome biogenesis is a highly complex process involving numerous proteins that assist in rRNA modification, ribosomal protein modification, and ribosome assembly, despite not being part of the mature ribosome. Although these factors are highly conserved across bacteria, many are individually dispensable without an apparent fitness cost. We hypothesize that ribosome assembly can proceed through multiple alternative pathways, such that deleting a single modification enzyme or assembly factor blocks only one route to a functional ribosome. To uncover the true functional importance of these genes, we generate large combinatorial libraries of strains carrying multiple gene deletions. By identifying synergistic genetic interactions, we aim to define the precise roles and redundancies of ribosome biogenesis factors.

Engineering microbial model systems for human ribosome function

Human cytoplasmic and mitochondrial ribosomes form the core of protein synthesis in our cells, and mutations affecting translational components are associated with a range of genetic disorders, including increased cancer risk. However, there is currently a lack of simple in vivo systems that enable high-throughput modification and functional analysis of human ribosomes. To overcome this limitation, we are developing microbial model systems in which components of the human translational machinery are introduced into single-celled organisms using CRISPR-based gene replacement strategies. These engineered systems aim to combine the experimental tractability of microbes with the biomedical relevance of human translation, providing a powerful platform for studying disease-associated mutations.