Lena Pernas received her bachelor’s degree from UCLA and Ph.D. from Stanford University. There, she worked with John Boothroyd to eludicate how mitochondria and the human parasite Toxoplasma gondii physically interact, and how chronic toxoplasmosis affects human immune responses. After receiving her Ph.D., Lena joined the lab of Dr. Luca Scorrano at the University of Padua where she studied how mitochondria counteract microbes. Her lab at the Max Planck Institute for Biology of Ageing is interested in the mechanisms by which an infected cell actively rewires metabolic processes and organellar function to defend against the challenge of microbial infection, and how human metabolism affects disease progression.

To generate energy, mitochondria consume nutrients that invading microbes depend on. This competing interest predicts an inverse relationship between mitochondrial health and microbial fitness. Although several pathogens disrupt host mitochondrial function, it was unknown whether  mitochondria act to impede pathogen replication.

As a PhD student in the lab of Dr. John Boothroyd, I identified the molecule that enable mitochondria to recognize and bind to the human parasite Toxoplasma gondii, which infects ~1/3 of the world’s human population. The dramatic changes I observed in mitochondrial shape during Toxoplasma infection led me to ask if mitochondria actively defend cells against microbes (contrary to the dogma that mitochondria are targets for microbes)? To address this question, I moved to the mitochondrial biology unit of Dr. Luca Scorrano where I discovered that host mitochondria act as nutrient competitors to Toxoplasma, and limit the parasite’s growth by restricting its access to host lipids. This work showed that mitochondrial metabolism functions as an innate immune-type defense and sheds light on how we can harness metabolism to develop anti-microbial therapies.

Arnau Sebé-Pedrós did his PhD (2009-2014) under the supervision of Iñaki Ruiz-Trillo at the University of Barcelona (Spain), investigating the origin of animal multicellularity from a comparative and functional genomics perspective. Then, I spent four years (2015-2018) at the Weizmann Institute of Science (Israel), working with Amos Tanay on single-cell analysis of animal cell type diversity and genomic regulation. Since 2019, I am a Group Leader at the CRG, within the Systems Biology program, where my group investigates the origin and evolution of cell type programs and associated genome regulatory novelties (transcription factors, enhancer elements, chromatin architecture).

Arnau Sebé-Pedrós is an evolutionary biologist interested in how genome sequence and its regulation translate into specific cellular phenotypes and, in particular, how this genotype-cell phenotype link evolves.

Cell types are the basic functional units of multicellular organisms. Distinct cell type transcriptional programs are deployed by regulatory mechanisms that control the differential access to genetic information in each cell. This genome regulation ultimately results in specific cellular phenotypes. However, the origin, diversity, and evolution of cell types and genome regulation remain largely unexplored. What are the regulatory mechanisms linked to the origin of cell differentiation? When did major animal cell types such as neurons emerge and did they evolve more than once? How do animal cell type gene regulatory networks evolve? And how these genetic changes translate into cellular novelties?

To answer these and related questions, in my group we combine chromatin profiling, proteomics, and single-cell technologies with computational genomics in order to dissect and compare cell type programs and genome regulatory architectures in phylogenetically diverse systems. This study has two major potential impacts. First, by systematically characterizing cell type diversity we advance our understanding of organismal evolution, function, and adaptation. Beyond that, the comparative study of these animal cell type programs can offer transformative insights linking classical models of molecular evolution with an intermediate molecular phenotype: cell type gene regulatory networks. Second, by studying genome function in non-traditional model species we can reveal fundamental, shared principles that govern cell biological systems and the associated molecular mechanisms of genome regulation.