האוניברסיטה העברית בירושלים
עמוד הבית
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חיפוש מתקדם
תכנית מד"ע : רשימת נושאים 2013

Proposed Research Topics - EMD Program 2013

 

Rotation

Communication

Research Theme

Name

No

02-6585406 

Office:
Silberman, 1-607

  Daphne Atlas

Our research group focuses mainly on developing new potential drug molecules for treating neurodegenerative related disorders such as Parkinson’s, autism, and Alzheimer’s disease.  Recently it was suggested that Alzheimer’s should be referred to as Diabetes type III and we study this correlation. Different cell cultures, Xenopus oocytes and amperometry are used to monitor changes in ion currents, and synaptic transmission during the onset of the disease. To study mechanistic aspects of synaptic transmission in relation to autism, we use molecular techniques, DNA mutations, viral infections, and apply dominant negative approaches.

Research Interests

Molecular biology (site directed mutagenesis) preparation of RNA, cloning, expression in oocytes; preparation of Semliki forest viruses; amperometry; electrophysiology, western blot analysis; biochemistry.

Techniques Used
Topic 1: What is the mechanism by which a single point mutation in the calcium channel, shown in Timothy syndrome causes autism? What is the relevance to sporadic autism? Can we reverse autism symptoms by a newly developed molecule?
Topic 2: Thioredoxin mimetics peptides as a potential therapy for neurodegenerative diseases such as Alzheimer’s, and investigating change in the brain function to explain why the probability to get Alzheimer’s disease is increased by 50% in diabetes.

Proposed Topics

No

02-6584192
054-8820512

Office:
Silberman, 3-443

(1) Biosensors for Environmental Pollutants
(2) Microbial Life in Extreme Environments 

  Shimshon Belkin

Research in the Belkin lab addresses several aspects of the interactions between microbes and their immediate environment. Two separate issues are currently addressed: (a) Molecular engineering of bacterial-based whole cell biosensors for the detection of toxic chemicals (including explosives); current research includes robotic high throughput molecular manipulations and accelerated evolution. (b) Analysis of the microbial populations inhabiting an extreme and fluctuating environment: the surfaces of a salt-secreting tree; molecular analysis of the leaf communities is carried out in parallel to physiological/biochemical studies of bacterial isolates.

Research Interests

Gene cloning, diverse approaches for enhancing gene expression; robotics-aided molecular evolution; reporter genes (bioluminescence, fluorescence); metagenomic analysis of natural microbial populations; bioinformatic analysis of microbial population structure.

Techniques Used

Topic 1: High-throughput molecular engineering of bacterial-based biosensors for the detection of buried landmines.
Topic 2: Molecular analysis of microbial populations in a fluctuating extreme environment.

Proposed Topics

Yes 

02-6584283 

Office:
Silberman, 3-515

Transcriptional Control of Nervous System Development

 Nissim Ben-Arie

The mammalian nervous system is composed of many cell types, which are born at a precise time, differentiate to a specific fate and migrate to an accurate destination. Our group is aimed at understanding how neuronal mother cells give rise to the numerous cell types. We focus on the role and function of bHLH transcription factors we discovered, which orchestrate the activation and repression of target genes regulating differentiation of developing neurons in the brain and spinal cord. The knowledge we gain is also applied to understanding of human diseases (developmental, inherited and cancer) and to development of tools for regenerative medicine.

Research Interests

We use a variety of methods in order to analyze molecules (DNA-RNA-protein), cells, tissues, organs and an whole embryo or animal. For example: molecular biology (cloning, genotyping, mutagenesis, real-time PCR, ChiP, RNAi, microarrays); histology (preparation of sections for microscopy, tissue staining, immunohistochemistry, in situ hybridization); in vivo models (generation and analysis of knockout and transgenic mice, overexpression in chick embryos by electroporation) microscopy (light, fluorescent, confocal); behavioral analysis and more.

 Techniques Used
Topic 1: Genetic, developmental  and transcriptional regulation of spinal cord development.
Topic 2: Molecular and behavioral analysis of mutant mice with midbrain abnormalities, as a model system for Parkinson’s disease
 Proposed Topics

Yes 

02-6586774

Office:
Silberman, 2-340

Biomedical Aspects of Human Pluripotent Stem Cells

 Nissim Benvenisty

The laboratory investigates the role of human pluripotent stem cells in tissue engineering, tumor formation, human genetic disorders, and human embryonic development (for more details, please see website).

Research Interests

Graduate students are involved in all aspects of human pluripotent stem cell research and use sophisticated genetic and cellular techniques. Techniques Used 

Topic 1: The tumorigenicity of pluripotent stem cells.
Topic 2: Modeling human genetic disorders using pluripotent stem cells
.

Proposed Topics

Yes 

02-6584320

Office:
Berman, room 114

Evolution and Mechanisms Underlying Sociality and Social Behavior

  Guy Bloch

Our research interests are focused on the evolution and mechanisms underlying social behavior and sociality. We study mainly honey bees and bumblebees as models. Bee social organization is astonishing; they live in well organized societies in which up to thousands of individuals coordinate their activities to achieve efficient division of labor, food gathering, colony protection, nest construction, and complex migratory (swarming) ventures. In spite of their relatively small and simple nervous system, bees exhibit complex social behavior, elaborate learning and memory capacities, sophisticated navigation skills, and in the case of the honey bee, also a symbolic (dance) communication system. To understand these complex behaviors we integrate analyses at different levels, including genomics, molecular, cellular, neuronal networks, individual behavior, and social organization. We have been studying diverse behaviors including phototaxis (directional response to light), reproduction, dominance, and sleep. Our major line of inquiry, however, has been the interplay between social factors and the biological clock for which the bee provide a superb model system.

Research Interests

Our lab is unique in its multi-level approach and ability to integrate diverse techniques ranging from molecular biology to sociobiology. These include, immunocytochemistry, protein blots (Western blots, immunopercipitation), PCR, Real-Time qPCR, dsRNA mediated gene silencing (RNAi), bioinformatics, RNAseq, endocrine manipulations, social manipulations of honey bee and bumblebee colonies, and diverse behavioral analyses.

Techniques Used
Topic 1: The interplay between social behavior, circadian rhythms, and sleep
Topic 2: The role of epigenetic processes in the regulation of complex social behavior

Proposed Topics

Yes 

02-6585123

Office:
Silberman, 2-430

Cell cycle control, neurodegeneration and ubiquitin

  Michael Brandeis

Our lab studies the role of ubiquitin in the regulation of the cell cycle and in neurodegeneration. All known cell cycle transitions are regulated by specific ubiquitin mediated degradation of cell cycle regulators. We are currently addressing a new, poorly studied, transition from cell division to quiescence. In a separate project we study how proteins that aggregate causing neurodegeneration like in Huntington’s and Prakinson’s diseases disrupt the ubiquitin homeostasis. We are particularly interested in how this could affect DNA damage responses and lead to cell death.All our work tries to image living cells in real time using state of the art microscopy methods.

Research Interests

Live cell imaging with wide field and confocal microscopes. Advanced methods of image analysis. Cell culture and manipulation (creation of cell lines expressing various fluorescent makers). Assays for DNA damage (Comet assay). Immunofluorescences and immunobloting. Molecular biology (cloning, generation of tagged expression vectors and site directed mutagenesis). 

Techniques Used

Topic 1: Watching neurodegeneration in real time.
Topic 2: The G1/G0 decision point.

Proposed Topics

Yes 

02-6585816

Office:
Berman, room 206

Evolutionary Developmental Biology

  Ariel Chipman

While the basic arthropod body plan is highly conserved, the success of the arthropods is due to the many variations on the basic body plan. In our lab we try to understand the evolutionary origin of this body plan, as well as how it has been modified in different arthropod groups over their evolutionary history. We focus on two avenues of research. One is the evolution of early patterning, trying to understand the evolution of the early events and the gene regulatory networks that define morphological areas in the arthropod body. The second is studying the processes that generate the segmented body plan, focusing on the function of the growth zone – the posterior area where segments are added during development.

Research Interests

Work in the lab circles around comparative developmental genetics, covering everything from the level of the entire organism and its body plan, through the level of regulation of individual genes, to comparative genomics and transcriptomics. Most of the work in the lab involves working with embryos and following gene expression, gene function and gene interactions, through in situ hybridization and RNAi mediated knockdown. proposed projects include cellular analysis, following cell division, cell movement and cell death in development. We are also increasingly using bioinformatics based approaches to discover novel genes involved in body patterning.
Techniques Used

Topic 1: Identifying novel genes involved in early patterning.
Topic 2: Cellular aspects of growth zone extension and segment generation.

Proposed Topics

Yes 

02-6586969

Office:
Silberman, 1-312

Molecular, Synaptic and Circuit Mechanisms of Plasticity Underlying Addiction and Compulsive Behaviors

Additional Information

  Ami Citri

We study how the nervous system encodes experience. Our main model system addresses the development of the response to cocaine experience. The multidisciplinary approach of our group applies knowledge gained from studying the principles of dynamic gene regulation, to investigation of neural circuit organization underlying the development of addictive behaviors. Understanding the mechanisms defining neural circuit organization in addiction will lead to unique insight into how the brain encodes experience and is expected to impact the treatment of psychiatric disorders.
The research in our lab is unique in its approach, combining detailed and comprehensive analysis of the transcriptional networks underlying the development of addiction in mouse models, with electrophysiological investigation of the relevant neural circuitry, utilizing cutting-edge techniques. This unique approach enables us to identify novel molecular and neural mechanisms and to investigate their relevance to behavior.
Projects in the lab span the spectrum from computational analysis of the organizational principles of transcriptional networks, through identification of the transcriptional and genomic processes underlying the development of addiction, to electrophysiological analysis of novel neural circuits and neuroplasticity underlying the development of addiction and other compulsive behaviors

Research Interests

Behavior; High-throughput qPCR; RNAseq; ChIPseq; Microscopy; AAV and Lentivirus manipulation of brain circuitry; Targeted whole-cell patch-clamp electrophysiology; Optogenetics; Computational analysis of transcription networks; Transgenic mice; Primary neuronal cultures.

Techniques Used

Topic 1: Investigation of gene regulatory networks underlying in-vivo cocaine experience.
Topic 2: A novel neuro-immune interaction potentially involved in addiction.
Topic 3: Functional investigation of the neural circuitry underlying feeding disorders.

Proposed Topics

Yes 

02-6584981

Office:
Silberman, 3-564

Cancer Epigenetics & Chromatin

Amir Eden

Since the completion of the human genome project, there is growing interest in heritable epigenetic information and its contribution to variation in the population, to normal cell function and to pathological conditions. At the molecular level, epigenetic regulation of gene expression is mediated through changes in chromatin structure and composition as well as by DNA methylation patterns.
Our lab is focusing on the causes and consequences of epigenetic alteration in cancer. Aberrant silencing of tumor suppressor genes (TSG) is frequently observed in cancer cells and is thought to play important role in cancer initiation and progression. In other cases, failure at the chromatin level results in aberrant activation of genes with oncogenic capabilities. Recent projects profiling the cancer genome and epigenome highlight the scope of this phenomenon, but understanding the cause of such events  and the molecular mechanisms involved in establishment and the maintenance of the epigenetic memory is lacking and is at the center of intensive research.
Our lab uses mouse models and engineered cultured cells to define the biological and molecular mechanisms driving epigenetic alteration in cancer in hope to translate this understanding into novel therapeutic approaches aimed at reversing cancer associated epigenetic aberrations.

Research Interests

All standard molecular biology and cell biology techniques are practiced in our lab including manipulation extraction and analysis of DNA, RNA and proteins. Tissue culture including embryonic stem cells, cell differentiation, reprogramming and more. Most our models are based on cultured mammalian but some work is done in vivo using mouse models. Special techniques include study of DNA methylation and chromatin using specific assays and genomewide high throughput sequencing such as ChIP-Seq and RNA-Seq. Some lab members focus on genome scale bioinformatic analysis of cancer genome and epigenome data.

Techniques Used
Topic 1: Causes and consequences of aberrant methylation in Cancer.
Topic 2: Sarcoma caused by defects in chromatin remodeling.
Topic 3: Transcriptome of replicating cells in vivo – cancer vs. normal replication.

Proposed Topics

Yes 

02-6594557 

Office:
Silberman, 2-313

Systems Biology of Transcription and Chromatin

  Nir Friedman

We aim to decipher the complex pathways that control transcription and how cells maintain their transcriptional state via chromatin.  These are central basic questions for many biological systems, including cancer and other human diseases. We use yeast as a model organism, since it provides for powerful genetics and experimental tools, and yet shares many of the basic regulatory and chromatin mechanisms with all eukaryotes.
Our main tool is using genetic screens to characterize mutations that impact the induction of stress-response genes. These screens are based on fluorescent tagging of target genes and measurement of protein induction by fluorescence microscopy/FACS. These screens are complemented by measurements of mRNA levels, chromatin modifications, and protein localization to characterize the interactions between cellular machineries involved in this regulation and understand their dynamics.

Research Interests

Yeast genetics, time-lapse microscopy, flow cytometry, and functional genomics assays (mRNA-seq, ChIP-seq). Automation (liquid handling robotics). Quantitative data analysis. Stochastic models.
 Techniques Used

Topic 1: Epigenetic memory: Finding genes involved in cross-generational stress adaptation.
Topic 2: Dissecting pathways that regulate nuclear localization of stress-activated transcription factors.
Topic 3: Chromatin and transcriptional noise: The role of chromatin in determining cell-to-cell variability in transcription.

Proposed Topics

Third rotation only

02-6585920

Office:
Silberman, 3-575

1. Developmental and Evolutionary Biology
2. Biotechnology

  Uri Gat

Our lab has several different and very unique lines of research:
In the main theme of developmental biology, a major project is to study the hair follicle mini-organ in an effort to understand how it forms and how it delivers its product – the structural hair. In recent years this skin appendage has become a most useful developmental model system for organogenesis, cell fate decisions, patterning and adult stem cell control focusing on several key genetic pathways and pivotal genes. One issue is to explore the cause of a rare genetic disease causing loss of hair as well as neurological defects.
In the evolutionary biology realm we explore the evolutionary origins of the above described genes and pathways. For this aim, we have introduced the sea-anemone Nematostella vectensis, which is a cool new model organism representing a simple basal metazoan. We are studying the primordial functions of developmental crucial genes in this animal and aim to uncover the mode of their emergence in evolution and their basic operation so as to better perceive their function in us.
In a biotechnological line of research we study a remarkable biomaterial, which like hair is also a protein based fiber – the spider silk. We have established a new expression system for the production and analysis of the structure of these extremely strong and tough fibers. Our approach has led to a better insight of the mode these fibers are made by self-assembly of their monomeric protein building blocks, and we strive to produce novel spider-silk fibers tailored for the use of man other than spiderman.

Research Interests

In the developmental studies we use many methods in the field including all types of biochemical assays, histological analysis, several antibody staining assays as well as production and/or analysis of Inducible transgenic and conditional knockout mice. 
In the evolutionary studies we use developmental biology methods including antibody staining and in situ hybridization as well as real-time PCR. The work also involves computational biology for genome and phylogenetics studies.
In the spider silk project we use many genetic engineering tools, biochemical assays and various chemical, physical and material science techniques for spider silk fiber analysis.
Techniques Used
Topic 1: Developmental biology and genetics of the hair follicles.
Topic 2: Evolutionary studies of key genetic pathways using the novel model animal - the sea-anemone Nematostella.
Topic 3: Studies of spider silk fiber formation and novel methods for their production.

Proposed Topics

Yes 

02-6586452

Office:
Silberman, 2-550

 Understanding the Mechanism of Cancer Development

  Michal Goldberg

In our lab we are studying early steps of cancer development. We study how cells respond to DNA damage in order to avoid cancer. By revealing this, we gain insights regarding cellular mechanisms that support the initiation of cancer. We study different aspects of cancer development, including causes of genomic stability, DNA damage response genes that when mutated will promote cancer development and the mechanism of DNA repair. Recently we started to identify novel candidate genes to be involved in breast and ovarian cancers and currently we are studying how these genes promote cancer. We also study how genes known to be mutated in different cancers support cancer development. An additional project in the lab is to study DNA repair and to reveal the interplay between cell cycle progression and the repair process. In addition we have several studies aimed to understand how genes that play a role in DNA repair, and thus protect against cancer, contribute to different cellular pathways.

Research Interests

We combine molecular, biochemical and cellular methods as well as bioinformatics in our studies: Human tissue-culture work, confocal and fluorescence microscopy, PCR, Western-blots, cloning, transfection, protein expression and purification, yeast genetics, mice model, immuno-precipitations etc.

Techniques Used
Topic 1: The connection between the circadian clock and breast and ovarian cancers. 
Topic 2: Live imaging of DNA repair.

Proposed Topics

Yes 

02-6585391 

Office:
Silberman, 3-468

Circadian Rhythms in Plants

 Rachel Green

All eukaryotes and many of the prokaryotes studied to date have endogenous ~24 hour “circadian” rhythms that are driven by an oscillator mechanism. In plants, the circadian system regulates a diverse range of cellular and physiological events from gene expression and protein phosphorylation to cellular calcium oscillations, growth and photosynthesis. The circadian system also plays a crucial role in monitoring day-length to regulate photoperiodic-dependant processes such as flowering. However, in spite of many years of research, much of the molecular mechanism of the plant circadian clock and its interactions with the environment are still unclear. In my laboratory we are working several projects with the aim of understanding the underlying machinery of the circadian system and its importance for plants.

Research Interests

DNA, RNA and protein analysis. Confocal microscopy. Transgenic plants. ChIP sequencing. Protein-protein interactions.

Techniques Used

Topic 1: Studying the pathways by which environmental signals entrain the plant oscillator (in collaboration with Prof. E. Huq (University of Texas). Our aims are to identify light entrainment pathway components by a combination of experimentation and mathematical modeling.
Topic 2: Understanding the circadian system at the level of individual cells.
Current opinion is that every plant cell has its own autonomous oscillator. However, most work carried out to date has focused on understanding the circadian system at the level of the whole plant. In our lab, we are have generated transgenic plants with modified circadian proteins to pioneer the study of the circadian system at the level of individual cells. Our initial experiments have shown that there are cell-specific differences in the plant circadian system.

Proposed Topics

Yes 

02-6585995, 02-6585191, 054-6586975 

Office:
Silberman, 2-428

1) the nuclear lamina and premature aging diseases.
2) Sensing and response of cells to elevated CO2 levels

  Yossi Gruenbaum

My group studies nuclear lamins and is using C. elegans as a model organisms to understand why mutations in the conserved lamin genes cause heritable premature human diseases. Previous studies in our lab have identified lamin complexes that are involved in various nuclear activities including the regulation of gene positioning and activity. We use these data to study the molecular mechanisms leading to both normal and premature aging and how lamins regulate cellular metabolism.
My group also studies the sensing and response of cells to high CO2 levels, which in humans are associated with pulmonary diseases. We found that prolong exposure to high CO2 slows down C. elegans developmental and causes fertility defects. It also leads to muscle deterioration, changes in gene expression and extended lifespan. We have identified a neuronal sensing response to CO2 that involves neuropeptide secretion. Currently, we dissect the molecular response of neuronal cells to elevated CO2 levels, try to identify the sensor molecule and how neuronal sensing is transmitted to muscle cells. Our lab puts a special emphasis on the working atmosphere in the lab and on the guidance of our new students

Research Interests

The study of both research subjects involves advanced techniques in molecular biology (generation and study of transgenic animals, molecular cloning, PCR, qPCR), microscopy (confocal, live imaging), biochemistry (proteomics, protein purification), genetics (genetic screens for novel genes and generation of new strains) and genomics (deep sequencing). Our study is performed on the levels of gene, organelle, cell, tissue and whole organismal levels.

Techniques Used
Topic 1: Understanding why mutations in lamin cause muscular dystrophy and premature aging diseases.
Topic 2: Neuronal sensing and response to high CO2 levels

Proposed Topics

 No

02-6585878

Office:
Berman, room-210  

  Dror Hawlena

Predation is a strong selection force regulating ecological processes. A key mechanism by which predators affect those processes is by stimulating defensive expressions of prey functional traits. Those defense expressions disrupt non-emergency functions, hence alter prey’s impact on ecosystems. Research in our lab explores those defense strategies and their ecosystem implications. We link food-web and biogeochemical concepts in an endeavor to generate predictive theory that explains context dependency in ecosystem functioning.    

 Reserach Interests

We study various model organisms in different terrestrial ecosystems, using manipulative field and laboratory experimentation, modeling, behavioral observations, and physiological measurements. We also use state-of the-art analytical techniques to measure stable isotopes and nutrient composition. 

Techniques Used

Topic 1: Consequences of predator induced physiological stress to ecosystem functioning
Topic 2: Self-regulation of desert ecosystems- the role predators play in controling activity of nutrient-vectors
Topic 3: The evolution and functionality of colorful tails in lizard hatchling

 Proposed Topics

Yes 

02-6585662

Office:
Silberman, 2-454

Plant Molecular Biology

  Yossi Hirschberg

Research in our group is focusing on genetics, biochemistry, molecular biology and genetic engineering in plants. We are using genetic and genomics tools to decipher the molecular regulation of carotenoid biosynthesis and its connection to fruit ripening, developmental processes and stress tolerance.
Our group pioneered the molecular analysis of the carotenoid biosynthesis pathway in plants. Over the years we have studied a number of carotenoid biosynthesis enzymes in order to understand the regulation of the pathway. We have utilized this knowledge to metabolically engineer tomato plants. Our research provided a paradigm of how natural diversity can be used to decipher complex biochemical pathways in plants. Such studies not only demarcate and define genes in the pathway, but also provide allelic diversity that can be used for research purposes or for breeding nutritional improvement of crop.
We have recently discovered a novel regulation of gene expression by cis-carotenoids. The molecular mechanism underlying this phenomenon is unknown.
Current research topics in our group aims at discovering the signaling mechanism of gene expression by carotenoids, understanding the regulation by the phytohormone abscisic acid (ABA) of plastid development and stress tolerance; analyzing structure-function of carotenoid biosynthesis enzymes, and cloning of new genes involved in pigment biosynthesis.

Research Interests

Gene discovery; Map-based (positional) cloning; Genes and genome sequencing; Plant genomics; Metabolic engineering (by genetic engineering in tomato); Plant genetics (mutational analysis); Secondary metabolism in plants (carotenoids); Protein engineering (site-directed mutagenesis, gene shuffling); Regulation of gene expression (mRNA analysis by microarrays and Affymetrix chips); Electron microscopy.     
Techniques Used
Topic 1:Molecular characterization of a new regulatory mechanism of gene expression in plants by cis-carotenoids
Topic 2: Using reverse genetics in transgenic plants to decipher the function of unknown genes whose expression is regulated by carotenoids
Topic 3: Biochemical analysis of a presumed carotenoid biosynthesis complex  

Proposed Topics

Yes 

02-6585099

Office:
Silberman, 1-322

A systemic view of circadian clocks: from gene expression to neuronal networks and behavior

  Sebastian Kadener

Circadian (24hs) rhythms in locomotor activity (sleep/wake cycles) are one of the best-characterized behaviors at the molecular, cellular and neural levels. Circadian clocks keep time by using sophisticated molecular machinery that includes transcriptional, post-trancriptional, as well as translational and post-translational regulations. In addition the circadian neurons in the brain are organized in a network and this organization is key for keeping a synchronous and coherent circadian clock. Circadian clocks are extremely robust systems. The main aim of our lab is to understand how and which molecular and neuronal processes contribute/generate/account for this robustness. For doing so we are mainly focusing on different processes regulating circadian rhythms robustness, mainly: 1) RNA turnover of central molecular components (i.e. by small and other non-coding RNAs); 2) communication of timing information among circadian neurons; 3) interaction of molecular pathways under normal as well as under perturbed conditions. In sum, our lab aims to integrate all these levels of regulation by using a multidisciplinary innovative approach that include beyond the state of the art techniques from the fields of Neuroscience, Molecular Biology, Genomics, Genetics and System Biology.

Research Interests

RNA biology (RNA-seq, RNA immunoprecipitation, PAR-CLIP, and others). In vivo monitoring of transcriptional activity from alive flies (by luciferase) or cultured brain (live imaging using confocal microscopy). Basic molecular biology (cloning, mutagenesis, analysis of gene expression, Chip-seq and others); Genetics of Drosophila. Behavioral assays of locomotor activity and videotaping of behavior. Analysis of miRNA expression and activity (by in situ hybridization, use of reporters, fluorescent sensors, RT-PCR, next generation sequencing, AGO-immunopurification). Genome wide screenings in drosophila cells by dsRNAs using high-throughput live microscopy. Immunocytochemistry and in situ hybridization in cells and drosophila brains and many other techniques.
Techniques Used
Topic 1: Interplay between molecular and neural mechanisms generating robust circadian rhythms in Drosophila.
Topic 2: Role of non-coding RNAs in the generation and maintenance of circadian rhythms in the Drosophila.

Proposed Topics

Yes 

054-2462875 

Office:
Silberman, 3-536

Spatio-Temporal Organization of Protein Folding and Aggregation: Studying Neurodegenerative Disease in Living Tissues One Cell at a Time 

  Daniel Kaganovich

Proteins are dynamic molecules and can adopt many correct and incorrect conformations at different conditions in the cell. Some of these conformations are either non-functional or can lead to aggregation, which causes different types of neurodegenerative conditions, including ALS, Huntington’s Disease, Parkinson’s, and Alzheimer’s Disease. Overall, the disease state is a rare phenomenon – most of the time cells can cope with protein aggregation and avoid toxicity. We study the way in which cells prevent the accumulation of damage at the level of protein structure, in order to understand not only goes wrong in disease, but also what goes right for many decades leading up to it. We study the protein quality control system in live cells and animals, at near-single molecule resolution using 4D imaging and super-resolution imaging. 

Research Interests

Super–resolution microscopy (Structured Illumination or SIM) in live cells. Total internal reflection (TIRF) imaging of single molecules on cell membranes. 4D confocal imaging of proteins in living cells over long time periods. In vivo biochemistry (tracking sub-populations of photoswitchable proteins in live cells over time); split fluorophore and FRET approaches to visualizing protein-protein interactions in live cells. High-throughput yeast genetics. Optogenetic interrogation of the cell biology of neural circuits in live worms using 4D imaging.

Techniques Used
Topic 1: Super-resolution and 4D imaging of protein aggregation quality control in yeast and C. elegans.
Topic 2: Studying neurodegenerative disease one neuron at a time in a C. elegans model of neural function and disease.

Proposed Topics

Yes 

02-6585234

Office:
Silberman, 3-419

 Mechanisms That Drive Ecological Processes

  Aaron Kaplan

We are mainly interested in the mechanisms that drive ecological processes such as the response of photosynthetic microorganisms to changing environmental conditions and those which determine the dynamics and composition of phytoplankton assemblages. Research our group have led to: 1the identification of the physiological and molecular processes involved in the CO2 concentrating mechanism of phytoplankton; 2intra- and interspecies communication with the aid of secondary metabolites including the biological role of cyanobacterial toxins and regulation of their biosynthesis; 3the cascade of events from oxidation stress to phytoplankton programmed cell death; 4acclimation of phytoplankton to the harsh conditions in desert crusts and the mechanisms whereby excess light is dissipated in their photosynthetic machinery. The topics proposed below are provided as an example.

Research Interests

Physiological, biochemical and molecular experimental approaches Techniques Used

Topic 1: Communication within the water body: can we eliminate toxin production in fresh water lakes- Lake Kinneret as a model system
Topic 2: What makes a green algae isolated from desert crusts the fastest growing algae

Proposed Topics

No

02-6585689

Office:
Silberman, 2-590

Human Genetics: Genetic Diseases and Cancer 

  Batsheva Kerem

Relevant for Topic 1 Chromosomal instability is a hallmark of cancer leading to mutations that promote the development of the cancer. We have recently found that this instability is caused by perturbed DNA replication, due to insufficient nucleotides required to support normal DNA replication (Bester et al. Cell 2011). Despite these new enlightening discoveries, the molecular basis underlying the differences in DNA replication between normal and tumor cells remains unknown. Moreover, the consequences of the replication perturbation to the tumorigenic fate of the cells are still elusive. In the proposed project we will explore how cancer genes and environmental factors lead to uncoordination between key genes/pathways regulating DNA replication and cell proliferation.
Relevant for Topic 2
Cystic fibrosis (CF) is a highly prevalent lethal recessive disease with 1:2500 live birth worldwide. As of today, over 1800 different mutations disrupting the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function were identified worldwide. Among them 10-15% mutations affect the correct splicing of the gene transcripts. Our goal in this project is to develop a novel splicing modulation approach for the treatment of splicing mutations in the CFTR gene, which is expected to augment correct splicing, improving CFTR function and patients' clinical state.

Research Interests

We are using in the lab tissue culture cells as model systems. We use standard molecular biology tools as well as bioinformatic tools. For the cancer projects (see below) we are using a high resolution unique approach of DNA combing, which allows the analysis of DNA replication in single DNA strand. This powerful approach enables us to investigate DNA replication in cancer cells and understand the molecular basis for replication perturbation in cancer. 
Techniques Used
Topic 1:  The molecular basis of early stages of cancer development
Topic 2:  Development of a new therapeutic approach for cyctic fibrosis by splicing modulation.

Proposed Topics

Yes 

02-6585233 

Office:
Silberman, 4-317

Mechanisms for Dynamics Response in Photosynthetic Organisms under Real World Conditions.

  Nir Keren

Photosynthetic organismsevolved to function under suboptimal conditions. Operating under such conditions require unique capabilities. Work in our laboratory focuses on the mechanisms that enable survival of photosynthetic organisms in limiting and extreme environments. Our research combines environmental aspects of global photosynthetic activity, physiological, biochemical and biophysical studies of plants and algae. Beyond basic science, we partner with applied physics researchers in an effort to implement biophysical concepts into the design of advanced solar cells.

Research Interests

Topic 1: Systems biology of transition metals in cyanobacteria: Transition metals play a key role in photosynthetic productivity. Their cellular concentrations are tightly regulated and the hemostasis pathways crosstalk. Work on this requires spectroscopic measurements of photosynthetic activities, Analytical chemistry analysis metals, biochemical and molecular biology studies of transporters and regulators of metals.
Topic 2: Functional dynamics of the photosynthetic apparatus in 3D: The photosynthetic apparatus function within the confines of a highly organized membrane system. The dynamics of this system have never been resolved. In this project we are developing tools for studying membrane dynamics in vivo using solution x-ray scattering techniques. Using this method we can look at time resolved changes of the 3D structure and couple it with photosynthetic activity. Students participating in this project will need to develop an understanding of optics, physical chemistry and biophysics. This project is carried out in collaboration with Prof. Uri Raviv from the Chemistry institute.

Proposed Topics

Yes 

02-6586543

Office:
Silberman, 2-435

Desert Plants: Physiology, Cell Biology & Genetics 

  Alex Levine

Plants Stress: adaptation to environment
Plants must constantly adapt to changing environmental conditions, but while most plants can grow in extreme conditions when stress develops slowly, they collapse during abrupt exposure. Thus, plants possess an inherent (genetic) capacity to adjust to stress through regulation of signaling networks.
We are studying plant signaling networks that regulate responses to biotic (pathogenic) and abiotic (environmental) stresses. All stresses are associated with major alterations in protein and membrane functioning. We showed that stress development is coordinated with other cellular processes, such as production of reactive oxygen species (ROS), ion fluxes and gene expression by lipid phosphoinositides. All these responses are regulated by intracellular vesicle trafficking system that is conserved among all eukaryotes, including similar signaling pathways. What is more, the outcome from applied stress can be changed by altering traffic.
We are especially interested in oxidative stress associated with salinity and cold temperature. While previously ROS were considered just toxic, we showed that ROS (inc. their subcellular localization) have a role in signaling transduction of adaptation resposnes. We also showed that the vesicle/membrane trafficking regulate the NADPH oxidase.

Research Interests

We are using molecular genetics (mutants and gene overexpression) and confocal microscopy of endomembranes and GFP-labeled protein marker s trafficking.

Techniques Used

 Topic 1: The role of vesicle/vacuolar trafficking in the adaptation of plants to the desert.

Proposed Topics

Yes 

02-6585161; 02-6585144

Office:
Silberman, 2-541

Stem Cell Chromatin

  Eran Meshorer

The Meshorer lab focuses on single cell and genome-wide approaches to understand chromatin plasticity and epigenetic regulation in embryonic and neuronal stem cells, during neuronal stem cell differentiation and reprogramming, and in pluripotent models of neurodegenerative diseases (e.g. Huntington’s disease; Machado Joseph disease). The Meshorer lab is working toward an integrative approach to the study of chromatin and epigenetic regulation in stem cells and pluripotent models of poly-glutamine-related diseases. By combining sophisticated imaging techniques at the single cell level and genome-wide approaches, the Meshorer group aims to provide deep understanding of chromatin-related regulation in stem cells, reprogramming and neurodegeneration. International funding sources include European Research Council (ERC), Human Frontiers of Science Program (HFSP) and EU networks.
Recent publications:
- Melcer et al., Nat Commun, 2012
- Sailaja et al., Proc Natl Acad Sci U S A, 2012
- Gokhman et al., Nat Struct Mol Biol, 2013

Research Interests

Spinning disk live fluorescent microscopy;
Embryonic and neuronal stem cells and stem cell differentiation;
Reprogramming somatic cells to induced pluripotent stem (iPS) cells;
Chromatin assays; molecular and cellular biology;
Epigenomics; computational biology and high throughput assays;
Single cell assays;
Techniques Used
Topic 1  Screening for novel stem cell regulators
Topic 2:   Single cell heterogeneity in pluripotent embryonic stem cells

Proposed Topics

Yes 

02-6586952

Office:
Silberman, 1-637

Proteomics of Stress Response

  Dana Reichmann

As interdisciplinary lab we combine experiments and theory to understand principles of protein homeostasis and stress response.
Ability of cells to sustain and recover after stress conditions depends on a complex network of protein chaperones and co-chaperones. Here we address fundamental questions in a recently discovered subgroup of molecular chaperones, which includes redox-regulated chaperone Hsp33. This is a unique class chaperones that serve as the first line of defense in particularly problematic stress conditions that cause both widespread protein unfolding and inactivation of essential housekeeping chaperones. By using state-of-the art mass spectrometry methods combined with bioinformatics and biochemistry we aim to understand how does this eukaryotic chaperones work. We will characterize redox regulation and chaperone function of the first eukaryotic Hsp33 chaperone in parasites of the Trypanosomatid family, which are responsible for lethal human diseases. We will investigate the role of oxidative stress on the proteome of the trypanosoma. The final goal is to understand the mechanisms leading to Trypanosoma pathogenesis. The findings will pave the way for new lines of projects e.g., identification of novel redox-regulated proteins across three domains of life, characterization of evolution of intrinsically disordered proteins and use of the Trypanosoma Hsp33 as a drug target.

Research Interests

The research methodology in the lab include mass spectrometry, redox proteomics, protein biochemistry, redox biology, computational biology, molecular biology, protein purification, in-vivo crosslinking by using non-native amino acids, chaperone biochemistry in vivo and in vitro, fluorescence spectroscopy.
Techniques Used

Topic 1: Proteomic and Functional Characterization of the Redoxome of Trypanosoma Brucei parasite.
Topic 2: Unfoldomics of the cellular stress response:  Characterization and Identification of novel intrinsically disordered chaperones

Proposed Topics

 No

  02-6585992

Office:
Silberman, 1-339

 

Structure-Function Relationship in Membrane Proteins

 

Shimon Schuldiner

Two main projects deal with the question of Structure-function relationship in membrane proteins (for more details, please see website).
1. Molecular analysis of mechanisms of transport across biological membranes: neurotransmitter transporters and multidrug transporters as experimental paradigms. 
2. Transport mediated multiple drug resistance. Evolution of specificity and structure in multidrug transporters.  

 Reserach Interests

Molecular biology (site directed mutagenesis, directed evolution and more); microbiology (bacteria and yeast) for the identification of mutants and phenotype measurements; biochemistry, for purification and characterization of membrane protein; tissue culture, for evaluation of activity of neurotransmitter transporters.

Techniques Used

Topic 1: Evolution of specificity of multidrug transporters. Studies using directed evolution
Topic 2: Mechanism of action of neurotransmitter transporters: identification and characterization of amino acid residues essential for activity.

 Proposed Topics

Yes 

02-6584078

Office:
Silberman, 1-525

 Engineering of Protein-Protein interactions: from computation to cell 

  Julia Shifman

Protein-protein interactions are crucial for all cellular pathways, including signal transduction, DNA replication, transcription/translation, and multi-component protein assemblies. Hence, understanding and manipulating protein-protein interactions is of high interest for both basic biology and applied research, such as drug design. In our lab we develop new computational methods for design and manipulation of protein-protein interactions and we test our computational tools experimentally by expressing the designed proteins and testing them for binding. One goal is to predict mutations that enhance protein binding affinity and specificity. These methods could be used to re-wire cellular networks and to optimize therapeutic molecules. Second goal is to study how protein-protein interactions evolve in nature and how we could simulate this evolution with computational methods. The third direction in the lab is design of novel binding domains, small proteins that could be converted into antibody-like molecules and bind to any target of interest. Such novel binding domains could serve as inhibitors of any disease-associated protein-protein interaction and hence could be a potential lead for drug design against any disease. Our lab is a multidisciplinary group of people that include physicists, chemists, computer scientists, and biologists.

Research Interests

In our lab we use a number of computational and experimental tools. First, we develop various computational approaches for protein design and evolution. We are using a number of existing software packages and are developing algorithms on our own. Next, we use and develop new molecular biology tools for gene construction of the designed proteins. We then express and purify the designed proteins and test them for binding to their targets. Here the experimental methods include SPR, fluorescence, enzyme activity assays, ELISAs, cellular essays, and binding selections with phage and yeast display. Finally, we work towards solving the structure of our designed proteins using X-ray crystallography. 

Techniques Used
Topic 1: Design of novel binders domains, therapeutic agents against cancer
Topic 2: Design of therapeutic molecules starting from snake toxins

Proposed Topics

Yes 

02-6585396 

Office:
Silberman, 2-317

Genetics of Neurodevelopmental Diseases

 Sagiv Shifman

Our research group aims to identify and characterize genes involved in human neurodevelopmental and psychiatric disorders. Most of our research is currently focused on autism. Autism is a heterogeneous genetic syndrome characterized by social deficits, language impairments and repetitive behaviors. Though extensively characterized clinically, autism pathogenesis remains a mystery. We are developing and using new functional genomics technologies, cell biology and computational approaches to uncover neurogenetic pathways and mechanisms involved in autism. The combination of these approaches is expected not only to advance our understanding of the genetic basis of autism, but also to set a basis for studying other diseases.

Research Interests

Topic 1: A mysterious gene: what is the function of a gene that is critical for brain development, causes autism, and evolved rapidly in modern humans.
Topic 2: What could account for the incomplete penetrance and variable expressivity of mutations causing autism

Proposed Topics

Yes 

02-6585109

Office:
Silberman, 1-420

From Stress Responses to Neurodegenerative Disease: Exploring the Underlying Molecular Mechanisms

Additional Information

  Hermona Soreq

The research focus is on the mechanisms underlying Acetylcholine malfunctioning in muscle, nerves and blood cells, which entails neuromuscular, neurodegenerative, anxiety disorders and inflammatory diseases. Pre-mRNA processing and micro-RNA regulators involvement are approached by advanced transcripts profiling in human cells and tissues and cell and engineered mouse model validations. "Molecular signatures" will be developed by transcriptome analyses re-programmed embryonic stem cells from Parkinson's and Alzheimer's disease patients  and matched controls, and Cholinergic signaling impairments in the brain, blood cells and the intestine, are manipulated by Oligonucleotide-mediated therapeutics (currently in Phase 2 clinical trials).

Research Interests

Transgenic engineering, High-throughput sequencing, RT-PCR, immunochemistry and enzymology, oligonucleotides and lentivirus manipulations, cell cultures and mouse genomics, human genotyping tests.
Techniques Used
Topic 1: Identifying novel pathways involved in Alzheimer’s and Parkinson’s disease
Topic 2: Exploring cholinergic contributions to anxiety and stress reactions

Proposed Topics

Yes 

02-6584902

Office:
Silberman, 2-411

Telomeres and telomerase, genetic disorders of telomeres, non-coding RNA structure and function

  Yehuda (Dudy) Tzfati

Telomeres, the ends of the eukaryotic chromosomes, shorten with age and provide a biological clock that controls the cellular lifespan. Excessive telomere shortening accelerates aging, while telomere elongation extends the proliferation potential but may facilitate cancer development. Telomeres are elongated by the enzyme telomerase. Telomerase is a ribonucleoprotein complex composed of several proteins and a non-coding RNA with essential structural motifs. The three-dimensional structure of the telomerase complex and its mechanism of action are largely unknown. We are using a budding yeast model and an in vitro reconstitution system for active telomerase to identify and study the three-dimensional structure and function of conserved domains of telomerase RNA.
To understand how telomeres protect the chromosome ends and control cell proliferation, we are using a yeast system where we can mutagenize the telomeres and disrupt their function. We are also studying a fatal telomere dysfunction disease termed Hoyeraal-Hreidarsson syndrome. We identified novel mutations in a gene not known previously to cause the disease, and we are employing cell lines derived from patients to study how these mutations cause the disease.

Research Interests

Standard molecular biology techniques, in vivo mutagenesis, yeast genetics, RNA techniques, single molecule fluorescence resonance energy transfer (smFRET), computer structure modeling, whole exome capture and deep sequencing, human cell culture, genetic analysis, gene therapy in human cells, immunofluorescence (IF) and fluorescence in situ hybridization (FISH).

Techniques Used
Topic 1: The genetic and molecular basis for the telomere disorder Hoyeraal-Hreidarsson
Topic 2: The mechanism of telomere synthesis by telomerase

Proposed Topics

Yes 

02-6585731

Office:
Silberman, 2-426

From Genes and Neurons to Behavior

  Alon Zaslaver

We are interested to understand the design principles by which genes and neural circuits dictate behavior. We focus on computational aspects of neural networks and how these computations change during network plasticity. For example, during Learning and Memory (how memory is stored and how it is retrieved), or during Aging and Neurodegenerative Diseases (how neural function is modulated as these processes progress?). To address such broad and fundamental questions we use C. elegans worms as a model organism, relying on its compact (302 neurons in total) and fully-mapped neural network.

Research Interests

We employ multi-disciplinary approaches combining experiments and computation. Experimentally, we work on multiple levels ranging from gene expression and single neuron dynamics to functional analysis of neural circuits and behavior. We use state-of-the-art optogenetic techniques to manipulate neural activity and behavior, and measure functional dynamics in the network in a single-neuron resolution. Using molecular techniques we zoom into the genetic components of individual neurons. As an interdisciplinary lab, we welcome excellent enthusiastic students from various backgrounds including Biology, Chemistry, Physics, CS and Cognition.

 

Topic 1: Learning and memory – where is the memory stored and can we artificially (optogenetically using light) activate and retrieve the information?
Topic 2: How animals encode and integrate the perplexing external world? how genes and neurons sense the environment directing animals to make (hopefully) the right decision?
Topic 3: Behavioral variability – why do we all behave so differently? Is it because of differences in gene expression levels? Is it due to variability in neural activity? Both?

Proposed Topics



 
 
המכון למדעי החיים ע"ש אלכסנדר סילברמן הפקולטה למדעי החיים האוניברסיטה העברית בירושלים האוניברסיטה העברית בירושלים