Max Planck Society Yearbook Highlights

_{Every year, the Max Planck Society selects exemplary scientific research reports from its institutes to highlight the breadth of research conducted within the society. The following are selected articles about the research at the Friedrich Miescher Laboratory of the Max Planck Society.}

Understanding why individuals differ from each other is a major goal in evolutionary biology. We study the genome of fruit flies to uncover which and how many genes regulate phenotypic variation, and integrate environmental perturbations to answer a key but still unresolved question: does the function of a given gene depend on the environment? Using whole-genome sequencing of thousands of individual fruit flies we identify the genes that regulate lifespan in low and high sugar diets and ask: are the genes that determine how long an individual lives the same ones in both diets?

In order to generate haploid gametes, eukaryotes can undergo a specialised form of cell division called meiosis. During the first round of meiosis, homologous chromosomes - one from each parent) - must be linked together so they can be properly segregated. In order to do so, most organisms use meiotic recombination to generate crossovers between homologous chromosomes. We describe our recent work that has used biochemical reconstitution to understand parts of the protein machinery that ensures faithful segregation of homologous chromosomes during meiosis.

Genome sequencing holds the key to fighting disease and understanding biodiversity. However, current techniques only produce sequence fragments and omit its context, sometimes causing misleading results. We have developed haplotagging, an improved method for highly accurate sequencing at low costs while preserving the sequences context. Haplotagging can be applied to identify a single gene present in two different butterfly species living between the Amazon and the Andes which creates a unique wing pattern.

We use an interdisciplinary approach combining computational chemistry, biophysics, and developmental biology to create new signaling activators and inhibitors. We have designed novel hematopoietic growth factors and antagonists of cancer-relevant signals, and their structures are in atomic-level agreement with our theoretical predictions. Strikingly, the growth factors are highly active and can induce the differentiation of blood cells in living zebrafish embryos. This strategy holds great promise to engineer signaling molecules with novel functionalities for future clinical applications.

Genetic variation is the basis of biodiversity, and is the key substrate of evolution. We are studying meiotic recombination, a key source of genetic variation, to elucidate on the role it plays while organisms adapt to new environments. Using linked-read genome sequencing technology, we have developed a method of studying recombination in individuals, and are using this to identify its molecular basis. Research on this fundamental process has implications for our understanding of first trimester abortion, genome function and how molecular mechanisms shape evolution in natural populations.

Sexual reproduction requires the generation of special cells called gametes, i.e. eggs and sperms, which carry half the genome of the parent. Meiosis is the process by which the parental genome is divided. In order to segregate the genome in a controlled way, novel linkages between sequentially similar chromosomes need to be created. Linkages are made by making programmed breaks in the DNA, followed by controlled repair of these breaks. Understanding the process of breakage and repair in detail at the molecular level will provide new insights into human fertility and genetic diseases.

How species differ from each other is a key question in biology. But genetic mapping between species has been challenging, because hybrid crosses are typically sterile. Combining latest stem cell and genomic techniques, the research group has pioneered in vitro recombination to circumvent breeding and directly cause gene exchanges in cells. In this way they have mapped differences between mouse species within weeks and created mouse embryos carrying hybrid mosaic genomes. By circumventing species barriers that prevent interbreeding this work sheds light on the genetic basis of trait variation.

The Max Planck Research Group Systems Biology of Development studies how signaling molecules transform a ball of cells into a patterned animal embryo. The scientists use an interdisciplinary approach combining genetics, biophysics, mathematics, and computer sciences. The results may help inform new regenerative medicine approaches for the generation of tissues from stem cells.

Organisms across the world show unique adaptations that enable them to survive and flourish in distinct environments. Researchers at the Friedrich Miescher Laboratory are studying stickleback fish to unravel the genetic changes which allow organisms to adapt and speciate in new environments. Marine sticklebacks have undergone an adaptive radiation with freshwater forms evolving repeatedly and independently at many different places. Using these powerful replicates of the evolutionary process, research is identifying the common molecular changes underlying adaptation and speciation.

House mice from the Faroe Islands are among the largest mice in the world. Researchers at the Friedrich Miescher Laboratory try to understand how they come to settle in the Faroe and how they have evolved island gigantism so rapidly in the last thousand years by sieving through their genomes. Hidden in the tapestry of the mouse DNA is a complex history resulting from hundreds of years of mixing between mouse subtypes. Efforts are now underway to uncover the genetics of island gigantism.

Plants and animals independently evolved multicellularity. To orchestrate the growth and development of their tissues and organs, both kingdoms of life use hormones. The research group investigates how plant receptor proteins sense a growth-promoting steroid hormone by combining structural biology and biochemistry with genetics utilizing the model plant Arabidopsis thaliana.

The nucleus, the command center of the eukaryotic cell, is separated from the cytoplasm by the nuclear envelope. At the beginning of cell division the nuclear envelope breaks down and DNA massively condenses to form chromosomes. The chromosomes are then equally distributed to the two emerging daughter cells. After this process is completed, chromosomes decondense and a new nuclear envelope is formed. The formation of the new nuclear envelope is a complex interplay of cellular membranes and proteins which scientists at the Friedrich-Miescher-Laboratory in Tübingen now try to understand.

During cell division, a multitude of changes has to occur concomitantly. Kinases, which have the ability to modify proteins by adding phosphate groups, play a crucial role during this process. Researchers at the Friedrich Miescher Laboratory have examined which proteins are modified by the Aurora kinase. This kinase is crucial for proper inheritance of the genetic information during cell division, and inhibitors of this kinase are currently tested in clinical trials. Elucidating the substrates of the Aurora kinase is therefore of both scientific and clinical relevance.

The development of novel high-throughput sequencing technologies allows the determination of the complete set of RNA-transcripts expressed under a given condition. Accurate and efficient computational methods are needed to uncover the full potential of the immense amount of data that is generated by these technologies. Our research group focuses on the analyses of transcriptome data using modern „Machine Learning“ algorithms, providing a better insight into the relation of genetic information and phenotypic traits of individuals.

DNA is packed into chromosomes. During cell division two daughter cells must receive identical sets of chromosomes containing the genetic information. Missing or extra copies of chromosomes might result in cell death and diseases, hence, complex cellular mechanisms ensure the equal distribution of genetic information during cell division. Scientists at the Friedrich Miescher Laboratory are trying to understand how the two halves of a chromosome are held together and subsequently are distributed to daughter cells.

The nucleus, the command centre of the eukaryotic cell, is separated from the cytoplasm by the nuclear envelope. How the nuclear envelope is disassembled at the beginning of cell division and how it is reassembled at its end, is largely unknown. The process is a complex interplay of cellular membranes and proteins. Scientists at the Friedrich-Miescher-Laboratory in Tübingen try to understand the underlying mechanisms.

When cells divide, the genomic information is duplicated and becomes symmetrically distributed to the daughter cells during division. Errors in the distribution of the genomic DNA can lead to cell death or promote tumor growth. Researchers at the Friedrich Miescher Laboratory use yeast to examine how cells ensure the extremely low error rate in the distribution of the genomic information.

Novel technologies allow for many measurements on biological systems, leading to fast-growing amounts and variety of data. In order to tap the full potential of the available data a thorough analysis is demanded. Apart from the electronic data organisation, an efficient and automatic analysis is a great conceptual challenge. Using modern Machine Learning Methods, researchers at the Friedrich Miescher Laboratory are analysing for example the complex phenomenon of cellular messenger RNA splicing. Their particular interest is the prediction of alternative splicing and a deeper understanding of its regulation mechanisms.

Membrane and protein transport are essential processes in the cell. Proteins have to be delivered to the correct cellular target compartment to fulfill their function. Most of the cellular organelles are surrounded by membranes in order to prevent uncontrolled mixing of their content with the cytoplasm. Communication between the organelles is mediated by vesicles that travel between different compartments. We investigate the regulation of membrane and protein traffic in different organisms. In the baker’s yeast Saccharomyces cerevisiae, we focus on the life cycle of a transport vesicle that is formed at the Golgi apparatus destined for the endoplasmic reticulum. In contrast, in the nematode Caenorhabditis elegans, we study membrane delivery into the division plane during cytokinesis. Cytokinesis is the last step in cell division: After DNA has been equally duplicated and distributed onto two poles, new membrane is inserted in between the poles at the plasma membrane which divides the cellular content, resulting in two cells.

The research group is working on two main areas of interest of Cognitive Developmental Psychology. On the one hand , there are studies being carried out to show how children process the multitude of information in the environment and whether changes in processing occur with increasing age (Information Processing). On the other hand, we aim to find out what kind of knowledge children have in the course of development and how they acquire this (Knowledge Acquisition).

Membrane and protein transport are essential processes in the cell. Proteins have to be delivered to the correct cellular compartment where they function. Most of the cellular organelles are surrounded by membranes in order to prevent uncontrolled mixing of the content of the compartment with the cytoplasm. The communication between the organelles is mediated by vesicles that travel between different compartments. We investigate the regulation of membrane and protein traffic in different systems. In the baker’s yeast Saccharomyces cerevisiae, we focus on the life cycle of a transport vesicle that is formed at the Golgi apparatus and destined for the endoplasmic reticulum. In contrast, in the nematode Caenorhabditis elegans, we study the membrane delivery into the division plane during cytokinesis. Cytokinesis is the last step in cell division. After the DNA has been equally divided and has been distributed onto two poles, new membrane is inserted in between the two poles at the plasma membrane, which divides the cellular content resulting in two cells that can start a cell-cycle anew.