In order to have a properly functioning brain, specialized brain cells called neurons need to differentiate to form input receiving dendritic arbors and output sending axons. Proper synaptic connection between dendrites/ dendritic spines and axons are essential for the wiring of the neural circuits. Failure to form or maintain these synaptic structures lead to neurodevelopmental or neurodegenerative diseases. A large set of cellular tools called proteins, encoded by coded genes, are at play for orchestrating neuron’s differentiation. Among these are kinases, enzymes that regulate all cellular processes via altering the activity of their substrates by phosphorylating them. My lab aims to discover novel kinase signaling networks in the dendritic development and synapse formation process in mice brain. We use electrophysiological recordings from brain slices, morphological analysis of dendrites and spines, novel chemical genetic methods to identify kinase substrates, cell biological assays and imaging to understand the cellular and molecular functions of kinase cascades in neurons. Our goal is to achieve a more detailed and broader understanding of molecular mechanisms that are at play in developing dendrites. Kinases are one of the most commonly targeted group of molecules for drug discovery, thus our work on kinases in dendrite development could also lead to identification of novel potential drug targets for therapies of neurological diseases.

Our immune cells combat thousands of infections by specifically recognizing individual pathogens. However, some pathogens escape the immune system and cause severe disease. We do not understand why our immunity falls short in these cases and are therefore unable to produce effective vaccines. Our research focuses on receptors on immune cells that directly recognize pathogens and trigger production of antibodies. By using novel imaging techniques we are visualizing the mechanisms of activation of these receptors by pathogens to reveal how pathogens escape immunity. In addition, we are investigating how mutations in these immune receptors contribute to the development of human lymphomas. We would like to use the outcome of this research to support the development of next-generation vaccines and anti-cancer agents.

The immune response to infection is regulated, both qualitatively and quantitatively by the CD4 T-lymphocyte, by their release of hormone-like substances or lymphokines, interferons or interleukins (IL-4, 5, 10) on encounter with pathogen or vaccine. We hope to understand at the molecular level the mechanisms that determine which type of interferon or lymphokine is produced by virus-specific T-lymphocytes on encounter with pathogen.

Tuberculosis is caused by an infection with a microorganism called Mycobacterium tuberculosis (Mtb) and is responsible for nearly 2 million deaths worldwide per year. Approximately one third of the world is exposed to the infection but only a proportion will develop active symptomatic disease. The people who do not develop active disease are thought to have a protective immune response and are termed "latent", but the nature of this protective response is not understood. The BCG vaccine, although used widely to protect against tuberculosis, has variable efficacy in protecting individuals against tuberculosis disease. Because the body's defensive response to tuberculosis has not yet been fully worked out it is difficult to create a successful protective vaccine as it is not known how to assess if a vaccine is effective. In addition, it is not known what part of the immune system is required to be stimulated and how, in order to provide protection. This study aims to search for differences in the body's response between asymptomatic latent individuals and infected individuals who develop active tuberculosis (pre and post-treatment). We will do this by looking at differences in the activity of all the genes in the blood of the infected individuals, those with and without disease, compared to healthy uninfected people. To ensure the gene activity is detectable in all the infected individuals, we will cause an exaggerated response by adding Mtb specific proteins before measuring the gene activity and we will also measure the gene activity at different times to see if there is a difference in gene expression over time. If a set of gene activities and/or proteins is present in the blood of asymptomatic latent individuals but missing in the blood of active tuberculosis patients after treatment this may represent a protective signature or fingerprint that keeps the latent individuals from becoming ill. Such a gene activity signature or fingerprint may be helpful in monitoring the efficacy of vaccines in the future. In addition, comparison of this protective gene activity in latent individuals with the gene activity in BCG vaccinated individuals, may reveal a unique gene fingerprint in the blood of latent individuals and provide information on a gene activity signature that may protect against adult tuberculosis, which the BCG vaccine does not always achieve. Once we have identified the differences in gene activity it may be possible to use this information to help monitor the host response during vaccination and so develop better vaccines to protect others from developing tuberculosis, if exposed to Mtb.

We aim to identify and characterize metabolic components from Mycobacterium tuberculosis responsible for its unique ability to survive in humans and cause disease. In addition, we are interested in understanding how antibiotics act against M. tuberculosis, how is resistance developed and how we can discover novel antibiotics that are better than the ones in current use. Enzymes are responsible for most of the activities in any cell, from bacteria to man. We are particularly interested in novel enzymes from M. tuberculosis that must participate in novel metabolic pathways. In addition, some of these essential enzymes will lack counterparts in humans and therefore might represent attractive new targets for antibiotic research. We are very interested in discovering how M. tuberculosis survives in host, evades the immune system and resist to antibiotic therapy. To achieve this, we are using state-of-the-art approaches to integrate several aspects of M. tuberculosis–host biology.