Department of biomolecular sciences
We are interested in how protein function is encoded in the structures of protein binders, enzymes, and antibodies. To test our understanding we computationally design new protein functions not seen in Nature and experimentally characterize these designs. Iterations of design and experimental characterization enable us to understand new features of how protein function is specified in Nature.
Our main research interest is to explore the interplay between the cellular metabolic state and circadian clocks and further identify the underling molecular mechanisms.
Our laboratory works on sphingolipids, important membrane components. We focus on two main areas: (i) sphingolipid synthesis and signaling, particularly of ceramide, and (ii) sphingolipid storage diseases, with an emphasis on mechanistic understanding of disease pathology and also on novel therapeutic approaches.
We study the basic physico-chemical principles governing the kinetics, thermodynamics and specificity of protein-protein interactions. The gained knowledge is translated into the development and implementation of protein engineering methodologies. Between other, these are used to study how the interaction of interferon with its receptors results in complex differential responses in cells.
With malaria continuing to be a major global disease, advances toward understanding the basic biology of P. falciparum remain essential. Our studies focus on different aspects of the cellular biology of the malaria parasite. In particular, we aim to explore cell-cell communication pathways between the parasites themselves and their human host.
We study the molecular mechanism and regulation of autophagy, a process responsible for the degradation of cytoplasmic proteins and organelles. A particular emphasis is given to the relationship of this catabolic pathway to disease such as cancer and neurodegeneration.
We ask how cells produce membrane proteins and how various structural determinants affect their function: (i) How ribosomes and mRNAs target the membrane, where localized translation of membrane proteins occurs. (ii) What dictates the fascinating capabilities of multidrug transporters and the multidrug-efflux phenomenon.
We are interested in deciphering the mechanisms by which extracellular and intracellular signaling queues affect ion channel function, both in excitable and non-excitable tissues. We focus on three main areas: 1) GPCRs-mediated ion channel regulation and modulation, 2) cellular mechanisms that control calcium homeostasis, 3) how physiological functions are affected by ions channels activity.
Studies in our laboratory aim towards elucidating the signaling mechanisms that mediate two cardinal activities of cytokines of the TNF family: induction of programmed cell death, and activation of transcription factors such as NF-kappa B that participate in the induction of immune defense mechanisms.
We aim to discover the mechanisms that control and coordinate the activity of molecular machines involved in the protein degradation pathway. To do so we apply novel native mass spectrometry approaches, in conjunction with fluorescence microscopy, biochemical and cell biology methods - generating an integrative mode of analysis combining in vitro and in vivo findings.
We study the interaction between peptides and proteins with and within the membrane milieu: These include: (1) selective cell destruction by innate immunity host defense antimicrobial peptides and lipopeptides future antibiotics; (2) the mechanism of HIV-cell fusion and how it evades the immune response; and (3) the role of transmembrane domains of cellular receptors (Toll-like receptors, TCR, ErB) in their proper signaling.
For tumors to expand, metastasize, and evade immune surveillance, genetically transformed cancer cells must recruit non-malignant cells, including macrophages, fibroblasts and endothelial cells. These cells, collectively termed the tumor microenvironment, are reprogrammed to support the tumor at the expense of its host. Our group aims to elucidate the mechanisms by which tumors reprogram their local environments. Our goal is to provide a deeper understanding of how tumors develop into systemic malignancies, predict which tumors are more likely to do so, and design therapeutic strategies to overcome these malignancies by targeting genetically stable elements in the tumor microenvironment.
Our studies focus on all aspects of the multi-enzyme cellulosome complex, which is considered the elite enzymatic system for conversion of cellulose and associated plant polysaccharides to simple sugars en route to biofuels, such as ethanol. For this purpose, we employ an array of multi-disciplinary strategies, including bioinformatics, genomics, biochemical and biophysical approaches, structure studies, and the fabrication of artificial “designer cellulosomes”.
We are investigating the mechanisms that govern the wiring of the nervous system during development, which includes axonal guidance, pruning and the role of local protein synthesis.
We are investigating long distance signaling mechanisms in neurons and other large eukaryotic cells, primarily an importins/molecular motor-based mechanism that integrates cytoplasmic and nuclear signaling. Currently our main focus is on the roles of this and related mechanisms in neuronal responses to injury and in cellular length sensing.
We are studying regulation of transcription and translation in health and disease. Specifically we investigate the mechanism underlying rapid transcriptional induction of NF-kappaB target genes, we analyze newly identified links between transcription, mRNA processing and translation and we study transcriptional control of microRNA genes and of embryonic stem cells.
The focus of our research is the beta cell of the pancreas.
We are interested in elucidating the mechanisms that control its unique ability to produce and secrete insulin in response to physiological stimuli, and in identifying the defects in this process that can lead to diabetes.
We study the structure and function of proteins, and of enzymes in particular, and how they evolve. To this end, we reproduce the evolutionary process of mutation and selection to generate proteins with new functions and structures.
We are studying molecular mechanisms of DNA repair, and in particular error-prone repair (translesion DNA synthesis) in mammalian cells. In addition, we employ the knowledge on DNA repair to develop novel functional enzymatic DNA repair biomarkers for risk assessment and prevention of cancer.
We are interested in transport processes and in photosynthesis. Within the realm of photosynthesis we are mainly concerned with dynamic processes that accompany the life cycle of the thylakoid network, including its response to different stresses and its formation and dismantling. Regarding nucleo-cytoplasmic transport, we are particularly interested in its selectivity, the behavior of the ensemble of transporting molecules as it relates to the transport of a single molecule and in applications to gene therapy. In both fields of study, we combine different approaches and methodologies including ensemble and single-molecule biophysical methods, biochemical and molecular biology techniques, statistical mechanical modeling and state-of-the-art electron microscopy.
We are interested in the universal process of membrane remodeling that occurs during endocytosis, when subdomains of the membrane are reshaped into cargo transport vesicles, which allow cells to take up material and communicate with the environment. Our studies focus on understanding the molecular mechanisms of endocytosis and their contribution to cell physiology. We use a combination of advanced imaging techniques that include correlated light and electron microscopy to visualize these processes with high spatial and temporal resolution. We are particularly interested in understanding how endocytic processes contribute to muscle differentiation and homeostasis.
We study epigenetic mechanisms by which developmental plasticity allows the environment to bring about heritable modifications in the developmental program. We approach this with a combination of in vitro (mammalian cells) and in vivo models (the fly, D. melanogaster), in which we confront developmental processes with unforeseen environmental challenges that promote deviations from the selected patterns of development.