Positions

We are interested in the universal process of membrane remodeling, when subdomains of the membrane are reshaped into functional structures that allow cells to take up material, sense and communicate with the environment. We are particularly interested in understanding how membrane ultrastructure is established during muscle differentiation and homeostasis.

The research in our group involves the study of cohesin-dockerin interactions, the assembly of the cellulosome components, enzymatic activity and analysis, protein design and structural characterization of cellulosomal modules. The motivated individual that will join us can gain experience in the following methods: cloning, expression and purification methods, biochemical and biophysical protein-binding measurements, crystallization and X-ray crystallography, and enzymatic activity assays.
Advantage: a good sense of humor.

Multidrug transport

Targeting of membrane protein mRNAs and ribosomes to the E. coli membrane

Our research is focused on elucidation of the means by which regulatory information encoded within the genes is decoded during transcription and translation and to reveal the connections between the two processes. To address these issues we utilize several biological systems. One is NF-κB, a major pro-inflammatory transcription factor. A subset of inflammatory-response NF-κB target genes is activated extremely fast following pro-inflammatory signal.

We are exploring signal transduction strategies using bacterial chemotaxis as a model. In chemotaxis of bacteria such as Escherichia coli or Salmonella typhimurium, the direction of rotation of the bacterial flagella is modulated so that the bacteria approach attractants and retreat from repellents. We are trying to understand how chemotactic signals are processed within less than a second, and how the response regulator of this system transmits this signal to the flagella. Of all the known signal transduction systems, this is the system that is best understood.

Observations made in our laboratory suggest that in humans, the egg and sperm communicate prior to fertilization by way of chemotaxis. This process is mediated by a factor secreted from the egg or its surrounding cells and detected by the sperm cells. We are trying to identify and characterize the chemotactic factors and their receptors on the sperm and to understand the molecular and physiological mechanisms of this process.

Study the role of autophagy in the regulation of different signaling pathways

Study different aspects of the mechanism involved in the formation and maturation of an autophagosome.

Study the role of TECOR2, a novel autophagic related factor.

Size matters, especially in neurons. Differentiated cells in higher eukaryotes exhibit a wide variety of shapes and sizes, while maintaining defined size ranges within cell subtypes. How do they do that? Genome expression must be matched to different cell sizes, with rapidly growing cells likely requiring higher transcriptional and translational output than cells in slow growth or maintenance phase.

Nerve axons are extremely long in cellular terms, extending many orders of magnitude longer than the diameters of their parent cell bodies. How then is the cell body informed of an injury in distant portions of the axon? We are working on the molecular mechanisms of long distance communication within neurons, and their implications for neuronal growth and regeneration. People can integrate to a range of projects within this theme. For an overview of our research topics please visit the group home page at http://www.weizmann.ac.il/Biomolecular_Sciences/Fainzilber/ .

Our lab uses computer algorithms to design the structure and sequence of proteins to obtain new function. We work on antibodies, enzymes, and membrane proteins. For more details on current research directions, please see our website: http://www.fleishmanlab.org/

See my web page for more details of our work

http://www.weizmann.ac.il/Biological_Chemistry/scientist/futerman/

We are an active lab with at least one opening for a rotation/MSC student

Current projects:
(1) Principles of operation of mammalian error-prone DNA repair.
(2) Analysis of novel genes involved in mammalian DNA damage tolerance.
(3) Effect of nuclear architecture on DNA damage tolerance in mammalian cells.
(4) Mechanisms and regulation of DNA repair in embryonic stem cells.
(5) DNA repair in risk assessment and early detection of cancer.

Malaria laboratory, Weizmann institute
We are seeking for highly motivated, committed and curious students to join our team as rotation students. The projects center on different fascinating aspects of the cellular biology of the malaria parasite.
Applicants with a strong background at the interfaces of molecular biology and/or biophysics are encouraged to apply. The chosen applicant will peruse wide spread of molecular biology technics, tissue-culture, microscopy, bioinformatics and more.
Candidate should send a cover letter and CV (includes a publication list) to Dr. Neta Regev-Rudzki.

Our group is interested in the changes that occur in photosynthetic organisms when faced with varying conditions. Whereas organisms are usually grown in the lab under constant, well controlled conditions, real life organisms face vast changes in their environment that occur at time scales ranging from seconds to months. The ability of photosynthetic organisms to efficiently utilize a capricious energy source such as ambient light is remarkable. Even more impressive is their ability to withstand stress conditions.

We are interested in signaling in excitable cells.
Ion channels physiology.
G protein coupled receptors signaling and regulation.
Ca signaling and homeostasis.

We are interested in signaling in excitable cells. Ion channels physiology. G protein coupled receptors signaling and regulation. Ca signaling and homeostasis.

Transcriptional reprogramming and stress responses in the tumor microenvironment

Molecular Biology, protein biophysics and bioinformatics

Investigating protein-protein interactions and interferon actions

Within the systems described, we study self- and hetero-assembly of membrane-bound peptides derived from membrane proteins. Interestingly, although it is generally accepted that the chiral nature of most biologically relevant macromolecules restricts specific interactions to “chiral partners”, we found that the lipid bilayer environment allows the interaction of two transmembrane (TM) domains with opposite chiralities, and between an all L-amino acid TM and its D,L-amino acid analog (diastereomer).

(i) Antibacterial and antifungal peptides - Living organisms of all types produce a large repertoire of gene-encoded antimicrobial peptides that serve as part of the innate immunity. Since 1991 we have established the “carpet” mechanism as an efficient model describing membrane permeation by many antimicrobial peptides. Most importantly, we disproved accepted dogmas on the role of specific structure, sequence or chirality in biological function. Furthermore, we found parameter controlling target cell specificity.

The mammalian innate immune response is responsible for the early stages of defense against invading pathogens. One of the major receptor families facilitating innate immune activation is the Toll-like receptor (TLR) family, type I membrane proteins. All TLRs form homo- and hetero-dimers within membranes and we showed that the single transmembrane domain (TMD) of some of these receptors is involved in their dimerization and signaling regulation.

1. The mechanism by which specific viral envelope proteins catalyze membrane fusion is still not fully understood. In recent years, we focused on gp41 and F, the envelope glycoproteins from HIV (retrovirus) and Sendai virus (paramyxovirus), respectively. Together with others we showed that: (i) unrelated viral families exploit similar fusion mechanisms (Peisajovich and Shai, 2003), (ii) membrane interaction induces drastic conformational changes in the fusion proteins leading to their participation in the actual membrane fusion event (Cohen et al., 2008; Sackett et al., 2006).

Studying the structure function relationship of protein complexes involved the protein degradation pathway

Studying large protein complexes involved in the protein degradation pathway using a novel mass spectrometry approach.

We focus on 1) the mechanisms underlying the embryonic development of beta cells both in vivo and in vitro and 2) the transcriptional and post-transcriptional mechanisms that permit beta cells to fulfill their role of releasing insulin in response to physiological needs.

Transgenic and conditional-knockout mouse models are applied to gain better knowledge of the physiological and pathophysiological function of the following signaling proteins that were discovered in our laboratory:
(a) Caspase-8, a cysteine protease that we have initially found to serve as the main proximal signaling protein in the initiation of death induction by the receptors (the extrinsic cell-death pathway), yet has more recently found also to serve various non-apoptotic roles.

Caspase-8, a cysteine protease discovered in our laboratory, is the main proximal signaling enzyme in the activation of the extrinsic cell-death pathway by receptors of the TNF/NGF family. In certain cells it also participates in the regulation of cell growth, differentiation and survival. A number of different human tumors, including small cell lung carcinoma, neuroblastoma, hepatocellular carcinoma, and others, are frequently deficient of caspase-8.

Positions are available joining the work on exciting ongoing projects in the lab:
1. The role of axonal mRNA translation during development.
2. Signaling mechanisms of axon guidance receptors.
3. Mechanisms of axonal degeneration