The genes in our DNA encode messenger RNA molecules, which, in turn, encode proteins. Proteins are the molecules in cells that perform most of the tasks that make life possible; they are the catalysts that make chemical reactions happen, they act as structural molecules that hold cells together, and they help other molecules such as nutrients move into and out of cells. Machines called ribosomes inside of cells read, or “translate,” the information in messenger RNAs to make the encoded proteins. When this process is not done correctly diseases such as cancer can result. In addition, when we are infected with a virus, the virus hijacks our cells’ ribosomes and associated protein synthesis machinery to make copies of itself. A deeper understanding of how protein synthesis works will facilitate attempts to cure diseases such as these. Our project aims to elucidate the structure of the protein synthesis machinery as it begins to assemble on an mRNA in preparation for making the corresponding protein. This information will help us in the same way that an automobile mechanic is helped by knowing the details of how an engine is put together; it will tell us which pieces go where, what they look like, and what each one does. These pictures will dramatically advance our understanding of this central biological process.

The proposed project aims to establish a new intercontinental, interdisciplinary collaboration between the Laboratory of Integrative Neuroscience, University of Buenos Aires, Argentina, headed by Prof. Mariano Sigman, and the visiting researcher Dr. Lisa Holper, Biomedical Optics Research Laboratory (BORL), University Hospital Zurich, Switzerland. Specifically we aim to introduce a new brain imaging approach by combining our novel portable, wireless functional near-infrared spectroscopy (fNIRS) instrument developed by the visitor’s laboratory with a 3D tracking device developed by the host laboratory. To show the potential of the new approach, we will conduct a pilot study focusing on two major advantages of fNIRS, namely reduced motion restriction in freely moving subjects and the possibility to simultaneously record from two interacting subjects. The experimental design will concentrate on fundamental cognitive-motor functions, by means of human cooperative versus competitive interactions, by monitoring two players in a simplified version of an air-jockey game. The actor’s and opponent’s cortical activation will be recorded by fNIRS in combination with a 3D tracking device to trace motions of the ball and the players’ hands. The context of the proposed collaboration offers a very challenging and exciting materialization of a technological advancement which will open a new vehicle for experimentation in neuroscience. The research visit aims to contribute both to the host laboratory’s technological achievements as well as the visitor’s clinical and scientific development.

The ability of a cell to produce all cell types of the body upon differentiation is known as pluripotency. In the early mammalian embryo, cells loose this capability to become restricted to a particular lineage. This loss of developmental potency occurs despite these cells possessing full genetic capability. It is thought that epigenetic alterations of DNA play a large part in this restriction process. This project aims to examine the role of epigenetic modification, specifically DNA methylation, in the maintenance of pluripotency and how this might be modified to restrict cells to a particular lineage.

On the basis of differential methylation patterns of gene promoters between pluripotent and committed cell types, several candidates for the regulation of pluripotency and lineage restriction have been identified (Farthing et al., 2008). Using novel techniques, other sites of differential methylation that likely affect early differentiation will be identified. Specifically, genome wide insulator sites that organise the three-dimensional structure of DNA and expression of neighbouring genes will be analysed for methylation changes during early development.

Genes affected in early development by changes in methylation at their promoter (identified by Farthing et al., 2008), or at nearby insulators (this study), will be tested for an effect on developmental potency by forced expression or knockdown in pluripotent embryonic stem cells. In doing so, these experiments aim to uncover a new understanding of pluripotency and how this might be manipulated for transgenic research and regenerative medicine, as well as provide novel insight into how the mammalian genome is interpreted.

Accurate segregation of the genetic material during mitosis is crucial for the maintenance of life. Chromosome segregation requires the formation of sturdy attachments between chromosomes and a microtubule-based structure named the mitotic spindle. The site of attachment of spindle microtubules onto chromosomes is named the kinetochore. Kinetochores are composed of 60-80 evolutionarily conserved proteins that form a structure up to 500 nm in diameter in metazoan cells. This is an order of magnitude larger than the largest macromolecular complexes such as RNA polymerase and the ribosome that are currently amenable to structural and enzymatic studies.

The characterization of the organization of kinetochores and their microtubule-binding activity is hampered by the inability to purify functional kinetochores from cells. The goal of our multidisciplinary international collaboration, therefore, is to reconstitute, from recombinant proteins, a functional kinetochore-microtubule interface. The microtubule-binding activity is provided by the so-called KNL1-Mis12 complex-Ndc80 complex (KMN) network, which contains ten proteins in three distinct complexes. Specifically, we propose to use an array of synthetic and analytic approaches to (i) rebuild the KMN network from purified proteins; (ii) evaluate how the immobilization of KMN network complexes on different nano-patterned substrates influences the ability to bind microtubules; (iii) study the dynamics of these arrangements using single-molecule fluorescence resonance energy transfer, total-internal-reflection fluorescence microscopy, and real-time atomic force microscopy; (iv) study the structural organization of the KMN networks by X-ray crystallography, electron microscopy and atomic force microscopy; and (v) test the significance of our conclusions for kinetochore-microtubule attachment in the genetically tractable yeast Saccharomyces cerevisiae.

We believe that our synthetic kinetochore-microtubule interface will eventually become accessible to the type of structural and enzymatic studies that continue to provide so much new understanding of the workings of other smaller biomolecular machines such as polymerases and the ribosome. Our studies will illuminate the process of kinetochore-microtubule attachment and will greatly advance the comprehension of the molecular bases of chromosome segregation.

Sensation of pain is triggered by specialized sensory neurons or nociceptors that display net-like processes directly beneath the skin. Unfortunately, the subjective nature of pain sensation, as well as the complexity of the underlying neuronal circuits in higher organisms makes it extremely difficult to study. Yet, essential principles of pain sensation could be analyzed in “simple” model systems such as Caenorhabditis elegans. This tiny nematode offers an unrivalled potential to use state-of-the-art technologies, as it displays just 302 neurons of which all synaptic connections are known. The sensory FLP and PVD neurons envelop the nematode with highly branched dendritic arbors and preliminary evidence indicates that conserved ion channels mediate specific responses of these neurons to “harsh touch” nociceptive stimuli. In this project, I will employ novel light-dependent regulators of neuronal activity (optogenetic tools), i.e. blue light-activated depolarizing Channelrhodopsin (ChR2), and yellow light-driven hyperpolarizing Halorhodopsin (HR), to define how the behavioural output of this FLP-PVD nociceptor network is evoked in living animals, and how it depends on physiological properties of the neurons involved. Furthermore, I will characterize putative nociceptive genes, as revealed by genetic analysis of PVD microarray profiles, by combining optogenetics, electrophysiology, optical Ca2+ imaging and (automated) behavioural assays using video tracking. My findings can provide key insights in pain sensation that are likely to apply also to higher organisms.

Most cancers originate from epithelial cells that have pronounced apico-basal polarity. Loss of cell polarity in these cells triggers tumor development. Against the tumor development, epithelia have an intrinsic mechanism that eliminates oncogenic polarity-deficient cells from the tissue, which acts as an “intrinsic tumor suppression”. In Drosophila imaginal epithelia, clones of cells mutant for evolutionarily conserved tumor suppressors, such as scribble or discs large, lose their polarity and are eliminated from the tissue. This elimination of polarity-deficient cells is caused by ‘cell competition’, the cell-cell communication-based cell elimination mechanism. When cell competition is genetically inactivated, polarity-deficient cells not only escape the elimination but grow aggressively and develop into tumors. Cell competition is thought to play an important role in organ size control, tumorigenesis, cancer progression, and maintenance of stem cell in the niche, but the underlying mechanism is poorly understood. The phenomenon in which ‘pre-malignant’ polarity-deficient cells are eliminated from epithelia by cell competition can be used as a ‘sensitized’ cell-competition assay system that has never been established. Using this system, I have developed a novel “non-cell autonomous” genetic screen system for identifying factors that regulate cell competition. In the proposed study, I will first take two parallel approaches, non-cell autonomous genetics and live-imaging approach, to dissect the molecular basis of cell competition, followed by a mathematical modeling to elucidate the universal principle of epithelial intrinsic tumor suppression governed by cell competition.

The unicellular eukaryote Plasmodium establishes malaria infection when parasites delivered by a mosquito bite invade and expand in the host liver. The onset of disease follows when these parasites spread to the blood. The initial parasite expansion within hepatocytes of the liver produces merozoites, the developmental stage of Plasmodium that infects erythrocytes and leads to disease symptoms. The infection of erythrocytes also results in the production of merozoites, thus propagating the blood stage of infection. The host cell pathways that are required for merozoite formation in either cell type and the mechanisms used by the parasites to manipulate these host pathways are largely unknown. The objective of this proposed research is to understand the molecular mechanisms by which Plasmodium parasites are able to create an environment that supports replication inside mammalian cells. To identify host pathways involved in merozoite formation, we will target candidate proteins with small interfering RNA in infected hepatocytes. In parallel, we will examine the association of host organelles with the intracellular Plasmodium-containing vacuole and determine the functional significance of any associated host compartment. To identify parasite proteins that usurp shared host cell processes in hepatocytes and erythrocytes, we will examine and characterize exported Plasmodium proteins produced during both stages of infection. Completion of the proposed research will identify host and parasite proteins important for Plasmodium infection of multiple mammalian cell types and help define the minimal requirements necessary to support intracellular parasite replication.

Mechanisms by which organ specific stem cells initiate differentiation (or cell cycle exit) remain largely unknown. In addition it is poorly understood, how cell cycle regulators post-translationally regulate organogenesis. I here propose to explore the link between the cell cycle and retinal development by examining the function and regulation of Id proteins (Inhibitor of differentiation) in retinal stem cells. By utilizing retina of medaka fish (Oryzias latipes), which is amenable to genetic and cell biological analyses, I will first determine the functions of Id in the proliferation of retinal stem cell. In addition, to complement limitations of the medaka retinal system with respect to biochemical analysis, I will be building on my previous expertise and will be using frog (Xenopus laevis) eggs to biochemically address the molecular regulation of Id. For this experiment, I will test two hypotheses concerning the interaction of Id with the APC/C, a ubiquitin ligase specifically degrading cell cycle regulators: (1) The APC/C destroys Id to allow differentiation of retinal stem cell, and (2) Id inhibits the APC/C to maintain stem cells with pluripotency. Finally, on the basis of the results from the Xenopus oocyte system, I will genetically test the models using the medaka fish retina. These results will allow developing the control of cellular differentiation by the cell cycle as new field in developmental biology, which will significantly impact also on other biological processes, such as diseases derived from genetic or developmental abnormalities.

Osteoclasts are the only somatic cells with bone-resorbing capacity and they play a critical role not only in normal bone homeostasis (called "bone remodeling") but also in the pathogenesis of bone destructive disorders such as rheumatoid arthritis and osteoporosis. A major focus of research in the field so far, however, has been on gene regulation by various cytokines, and several key questions about the mode of action of these cells in vivo have been less well studied, including the process of recruitment of osteoclast precursors to their workplace (bone surface) and regulation of terminal maturation. To address these issues, in addition to conventional experimental techniques including biochemistry, molecular biology, and gene-targeting, I am utilizing a new experimental method involving intravital two-photon microscopy for bone tissues that was developed during my postdoctoral research experience. One major subject of the planned work is better defining how the migration and positioning of osteoclast precursors is influenced by a combination of a lipid mediator (e.g. S1P) and chemokines (CXCL12 and CX3CL1). I also plan to analyze osteoclastogenic cell fusion and the role of cell-cell contact in osteoclastogenesis in vivo. Furthermore, recent computational biology advances will be exploited in this proposed study to develop a multiscale mathematical model of osteoclast behavior, helping us to better understand in quantitative terms how bone remodeling is maintained by osteoclast function. Beyond its basic implications, the findings of this multidisciplinary study may lead to insights into human diseases and contribute to new therapeutic strategies.

Heme, consisting of an iron atom contained in the center of a porphyrin ring, is one of the most important and versatile prosthetic groups of proteins in both prokaryotes and eukaryotes. However, when heme is released from proteins, it is toxic to cells. Detoxification of free heme is essential to the survival of malaria parasites. During the growth of malaria parasites within the red blood cell the parasite obtains nutrients by taking up and then digesting hemoglobin, which releases high quantities of free heme. The parasites convert free heme into an insoluble crystalline form called hemozoin that is not toxic to cells. Although several mechanisms have been proposed for the production of hemozoin, the molecular mechanism is highly controversial. Crystal structure of hemozoin is made of a cyclic dimmer of heme in which an iron-oxygen coordinate bond links the central iron of one heme to the oxygen of the propionate group of the adjacent heme. The reciprocal iron-oxygen bonds between two heme molecules are unusual and have not been observed in any other porphyrin dimmer, which could involve a particular kind of enzymatic reaction mechanisms. The objective of the present research project is to reveal the process of heme crystal formation in the parasites. I wish to develop a combined biochemical and biophysical approach to analyze the unusual enzymatic reaction of the hemozoin formation. Since the formation of hemozoin is essential to the survival of the parasites, elucidation of the molecular mechanism of the hemozoin formation will help to develop anti-malarial drugs.

Formation, homeostasis and function of tissues and organs depend heavily on a network of cell-to-cell signals that are transmitted through soluble molecules, cell surface bound and transmembrane proteins. Semaphorins and plexins are two protein families with central roles in cell-cell signaling. As such they are found in most tissues where they are often required for viability and involved in a wide range of processes such as guidance of cell migration, neural connectivity, cancer, angiogenesis and regulation of immune responses.

Members of the semaphorin family are secreted or cell surface bound proteins and as such can mediate both long- and short-range signals or act as receptors themselves. Plexins are large (around 1900 residues) single transmembrane spanning molecules and the most important receptors for semaphorins. Although much is known on the cellular function and effects of semaphorin-plexin signaling very little is known on the molecular mechanisms underlying this signaling system.

The goal of the proposal is to elucidate the molecular mechanism underlying semaphorin-plexin signaling. I will use a combined approach of biophysical analysis, cell based fluorescence and functional assays, and structural biology techniques to resolve in detail the structural and oligomeric changes during semaphorin-plexin complex formation and relate these to its functional properties.

Given the importance of semaphorins and plexins in a wide range of functions understanding of the molecular mechanisms and detailed insights into the interactions will be instrumental in the development of new therapies in neural regeneration, immune disorders and cancer.

Bacterial communities in the plant rhizosphere carry out functions that are essential to plant nutrition and disease suppression in terrestrial ecosystems. New cultivation-independent approaches using molecular tools now offer great promise for exploring the genetic diversity of these microorganisms and learning how bacterial communities function to support plant growth and root health. In the research described here, I propose to study the bacterial communities that are associated with the roots of the oldest living plants on Earth. These plants, Creosote bush (Larrea tridentata), are the predominant shrubs in the deserts of the S.W. USA, with some individuals having an age of more than 10,000 years. The long term selection and coevolution of microbial communities with the roots of these plants provides a unique opportunity to examine how certain bacteria may help plants to acquire nutrients and resist disease in poor desert soils, such as we share in the Atacama Desert in Chile and the Mohave Desert in the USA. To carry out this research, I will work with the Crowley research group at the University of California, Riverside, where we will use a metagenomics approach to characterize the bacterial communities and identify genes that encode potentially novel bioactive molecules. This research will provide me with valuable training in metagenomics, and will establish a new collaboration between our research groups. If we are successful, this research will further provide fundamental knowledge on how soil microbial communities function for adapting plants to harsh desert environments.

Many aspects of metabolism and behavior are controlled by circadian (24hs) rhythms. These rhythms rely on intracellular oscillations of clock proteins that have been proposed to be generated by interconnected transcriptional feedback loops. However, and despite the extensive work conducted in the past twenty years, it is still controversial how these clocks keep time. During my post-doc I established the importance of transcriptional oscillations for circadian timekeeping and discovered that miRNAs play a central role in circadian rhythms in Drosophila. miRNAs are small non-coding RNAs that serve as post-transcriptional regulators of gene expression. Through the development of new tools for the study of these small RNAs in fly heads, I was able to determine that the miRNA bantam is a central clock component and regulates the master circadian transcription factor Clk. In addition, I identified miRNAs expressed in the head circadian tissue. The present research plan aims to elucidate the molecular mechanism underlying circadian rhythms with special emphasis on the transcriptional and miRNA regulatory pathways. My specific aims are to: a) study a new transcriptional component of the circadian clock; b) characterize the post-transcriptional control of CLK mRNA; c) characterize temporally and spatially the expression and function of circadian relevant miRNAs. The present project will also deepen the current understanding of miRNA regulation and function in the brain. The HFSP fellowship was essential for the emergence of my current research project, and the CDA will provide the financial support and scientific independence to develop it.

The aim of this proposal is to develop a novel generalisable small molecule biosensor for the in vivo quantification of the phytohormones brassinosteroid and auxin in plant signalling. Although small molecules are universal informational signals, there is currently no available technology for monitoring their abundance in high temporal and spatial resolution. Since hormones are essential for plant growth and development, the model plant Arabidopsis thaliana will be used as a proof of concept system for developing and assessing a novel hormone biosensor, which will be engineered based on molecular evolution and rational design. Once a brassinosteroid and auxin sensor system is developed and validated, it can be utilised for investigating the highly interconnected networks of hormone signalling in plants in response to differential developmental stages and stimuli. Furthermore, the technology of the generalisable hormone biosensor can be applied to other model organisms and small molecules, thus enabling the detailed characterisation of small molecule induced signalling in any biological system.

Textbooks present motor memory as monolithic: once acquired, never forgotten. They dissociate it from declarative memory by suggesting that motor memory does not have a short-term form. However, recent theoretical and experimental results have overturned this view, suggesting that motor memory is supported by processes that have multiple timescales: fast processes that learn quickly but decay rapidly with time, and slow processes that are less sensitive to movement errors but show better retention. Indeed, it appears that formation of motor memory may be a gradual transformation from the fast to the slow processes, and this transformation may depend on time and the statistical properties of the learner’s performance errors. We propose to use this idea to shed new light on one of the fundamental problems in neuroscience: the distinct functions of the cortical motor structures vs. the cerebellum in learning and retention of skilled movements.

The unsolved problem is illustrated by two examples: whereas neurophysiological and neuroimaging experiments have found correlates of adaptation in the primary motor cortex (M1), functional disruption of this area by transcranial magnetic stimulation (TMS) appears to produce no effects on acquisition, yet produces post-adaptation amnesia, i.e., rapid forgetting. In contrast, while the cerebellum is crucial for adaptation, damage to this structure appears to spare some skills that were acquired before the damage. Our basic hypothesis is that the faster timescales of memory are dependent on the cerebellum, effectively learning to predict the consequences of motor commands and correcting the motor commands via internal feedback, and the slower timescales are dependent on the cerebral cortex, effectively learning to produce the motor commands appropriate for the specific conditions of the task.

Our project combines computational, psychophysical, neuropsychological, and neurophysiological approaches to investigate how time and statistics of performance. We will use common eye and arm movement paradigms in behavioral and neurophysiological experiments to explore how controlled changes in sensory and motor noise effect motor control and learning. This will enable us to directly relate high level behavior to neural mechanisms

Interstitial fluid flow strongly affects, in multiple ways, the structure and function of living tissues. Quantitative understanding of the effects of interstitial flow on cellular functions as well as on the interactions between cells and their environment during tissue development will improve the effectiveness of therapeutic treatment for native tissues, permit the efficient fighting off against persistent biofilm infections, and enable the successful engineering of functional artificial tissues. The proposed research project aims at the investigation of the effect of fluid flow on the spatiotemporal dynamics of bone cell proliferation and tissue development in 3D scaffolds confined within a microfluidic device. Visualization experiments will be performed under various flow regimes, such as transverse perfusion (which mimics the flow driven by the pressure difference between vessels in vivo) and parallel perfusion driven either by constant flow rate or by constant pressure drop. The response of bone cells to changes in the magnitude and/or the direction of the average fluid velocity through the scaffold will also be investigated. The experimental data will be analyzed and interpreted with the help of recently developed advanced theoretical models and computer simulation methods. In the context of this fellowship, I will have the opportunity to conduct research abroad on a very exciting and important scientific theme in one of the leading groups in tissue engineering, and to receive training on several experimental methods, including bone cell and tissue culture in 3D, confocal laser microscopy, and preparation of polymeric scaffolds.

The growth of animal organs is precisely controlled. When genes affecting growth, such as the Myc or Minute genes, are expressed unequally, competition is induced between adjacent cells. Cells that carry more copies of growth genes, divide faster than their neighbors within a tissue. Importantly, their growth advantages do not lead to an increase in tissue size because they trigger the death of neighboring cells in order to compensate for their own expansion. How cells communicate to achieve this is not known, however, regulators that limit tissue growth, such as members of the Hippo pathway, have been suggested to play a role. To identify components of the cell competition pathway, I propose to conduct a genome-wide RNAi screen in cultured Drosophila cells. To accomplish this, marked cell lines will be exposed to genetic knockdown and cultured with their wild-type counterparts. Assessment of relative overgrowth in one population, and death in the other, will identify novel candidates that induce or regulate cell competition. I will then test, in vivo, the genes identified from the screen in both developing tissues where competition has been documented, and ones where it has not. Importantly, candidates also will be investigated in tissues undergoing turnover in the adult to assess the role of cell competition in tissue homeostasis.

Plants make use of two-component systems for signal transduction, and these are involved in vital cellular processes such as the response to cytokinins, ethylene, red light, and osmosensing. Previous studies have been focused on functional characterization of two-component elements in plant signal transduction, in particular cytokinin signaling. To elucidate how two-component elements control various aspects of plant development, expanding analysis of the two-component pathway to other elements of the network is required.
My first aim is to identify novel transcription factors regulated by the two-component signaling pathway through genome-based screens. Based on previous results that the type-B response regulators (type-B ARRs) act as transcriptional regulators in the two-component pathway, I will isolate candidates showing altered expression in type-B arr mutant backgrounds. My second aim is to investigate the precise role of newly identified candidate transcription factors through physiological and molecular analysis. My third aim is to elucidate the connections between the two-component pathway and the other cellular networks by constructing functional/physical interaction maps among components. Through this study, I will contribute to an understanding of how the two-component gene network acts to alter plant growth and development..

It has been suggested that the large recognition diversity of cell surface proteins is required for complex neuronal wiring. Drosophila Down syndrome cell-adhesion molecule (Dscam) is a cell surface protein that belongs to immunoglobulin superfamily. Dscam can generate up to 38016 isoforms by alternative splicing and shows specific homophilic binding. Based on these features, Dscam is thought to be a very attractive molecule that could explain the mechanism of specific neuronal circuit formation. Dscam homophilic binding induces repulsion signaling and thereby contributes to dendritic self-avoidance and axon branching. However, the molecular mechanisms that translate adherent homophilic binding into repulsion are not understood. Here, I suggest to identify novel binding proteins of Dscam by biochemical method and to investigate their importance in vivo by genetic method. My host supervisor Dr. Schmucker has suggested that each Dscam isoform has non-redundant function during axon targeting of mechanosensory neurons. To examine this possibility, it is important to investigate expression pattern and localization of Dscam isoforms at protein level. To this end, I propose to use extracellular domain of Dscam isoform fused to a reporter protein such as protein phosphatase (AP). Next, I investigate whether intercellular Dscam-Dscam interactions could function as adhesion during axon/dendrite targeting and synapse development. To this end, I examine that whether same sets of isoforms are expressed at pre- and post-synaptic region and examine the role of Dscam in localization of neuronal transmitter receptor and synapse transmission.

Cell migration is driven by the polymerization of cytoskeletal proteins into filaments that push out the leading edge of the cell by a biochemically and biophysically complex process. The goal of our research is to provide an integrated picture of how the biochemical activities of cytoskeletal proteins affect individual filament mechanics and overall network properties to produce useful force and movement.

We will study two cytoskeletal protein machineries: actin of eukaryotic cells and Major Sperm Protein (MSP) of Caenorhabditis elegans sperm cells. Both machineries have very similar functionalities in terms of motile force and velocity, yet actin and MSP have different biochemical properties (sequence, structure, interaction partners) and thus likely different biophysical properties (mechanical stiffness and strength). By comparing these two very different cytoskeletal systems that have identical roles in cell movement, we hope to define the universal biochemical and physical properties governing cell motility.

To achieve this goal, we have assembled an interdisciplinary team that includes experts in actin and MSP biochemistry and in biopolymer mechanics on both the single filament and collective network scales. On the one hand, we will use biochemical manipulation and in vitro motility assays to test how biochemical regulation affects actin- and MSP-driven propulsion. The physical repercussions of biochemical tuning will be investigated by microrheology and scanning probe microscopy to measure the forces generated by polymerizing actin and MSP filaments and their elastic properties. For actin, we will focus on how certain domains and phosphorylation states of the Drosophila Enabled/Vasodilator-stimulated Phosphoprotein (Ena/VASP) family affect movement. The Ena/VASP proteins are key players in cell motility, but have been little studied from a mechanical point of view. For MSP, we will establish for the first time a purely in vitro motility assay and use this set-up to study MSP-associated factors that will be identified during the course of this project. This will be the first detailed biochemical/biophysical study of this propulsion system in the model organism C. elegans.

Ultimately protein chemistry and mechanical properties will be integrated into a complete description of cell movement in the context of two very different cytoskeletal systems.