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Avaliable Technologies

Category
Technology Name
Briefcase
Scientist
1549
A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one...

A tailor-made strategy for cancer treatment. The ErbB family of tyrosine kinase receptors and their ligands play important roles in development and tissue remodeling throughout adulthood. ErbB proteins are involved in several types of human cancer. Clinical studies indicate that over-expression of one or more ErbB ligands correlates with decreased patient survival. The currently approved drugs for the treatment of cancers driven by the ErbB family target the receptors rather than the ligands, and they include either monoclonal anti-receptor antibodies, or tyrosine kinase inhibitors (TKIs). Because of resistance and moderate clinical efficacies of anti-receptor antibodies and TKIs it is worthwhile considering alternative strategies. The present technology combines several antibodies, capable of blocking ErbB ligands, with chemotherapy.

Applications


  • Treatment of cancers that possess the ErbB receptors (e.g. colorectal, liver, bladder, and head and neck tumors)

Advantages


  • Effective blockade of the tumorigenic action of ErbB-specific ligands
  • The combination protocol may enhance the sensitivity to chemotherapy

Technology's Essence


In the outlined technology, monoclonal antibodies were generated against two ligands, namely TGF-? and heparin-binding EGF-like growth factor. Combining the two antibodies with a chemotherapeutic drug enhanced the ability of chemotherapy to inhibit pancreatic tumors in mice. Therefore, this technology offers a general cancer therapeutic strategy that entails profiling the repertoire of growth factors secreted by a tumor, and combining with chemotherapy several antibodies capable of blocking autocrine ligands, in a way that sensitizes tumors to cytotoxicity and delays onset of chemoresistance.

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  • Prof. Yosef Yarden
1783
Aluminum and magnesium alloys are gaining more recognition for light-weight materials applications. In spite of this, such alloys have not been used for critical mechanical applications mainly due to their inferior mechanical properties compared to other engineering materials such as steel. Hence, many...

Aluminum and magnesium alloys are gaining more recognition for light-weight materials applications. In spite of this, such alloys have not been used for critical mechanical applications mainly due to their inferior mechanical properties compared to other engineering materials such as steel. Hence, many researchers have attempted to reinforce these alloys and obtain light-weight materials with excellent mechanical properties. The reinforcement process of the alloy can be achieved by introducing another material to form metal matrix composites. Different studies show that such composites exhibit improved properties, such as increased yield strength and tensile strength, enhanced stiffness, improved thermochemical properties, etc. However, the introduction of nanomaterials into the metal matrix is rather difficult due to the harsh manufacturing conditions employed for processing the metal composites.

The group of Prof. Reshef Tenne has developed state-of-the-art aluminum- and magnesium-based metal matrix composites, comprising small amounts of inorganic nanomaterials, such as nanotubes and spherical nanoparticles. The new nanocomposites exhibit much superior mechanical properties compared to the pristine alloy.

Applications


·         Automotive, transportation, and aerospace industries

·         Jet engine technologies

·         Electronics

·         Medical technologies


Advantages


·         Light-weight metal alloys

·         Excellent mechanical properties

·         Straight-forward fabrication technique


Technology's Essence


Aluminum (AA6061) and magnesium (AZ31) alloys were combined with small amounts (up to 1 wt.%) of either tungsten disulfide nanotubes or inorganic fullerene-like tungsten disulfide nanoparticles to form metal matrix composites using a melt-stirring reactor operated at high temperatures (up to 750oC). These nano-structures exhibit unique mechanical properties, which make their usage as composite fillers very promising, and a remarkable stability at elevated processing temperatures. Despite the small amounts of added nanostructures, their addition led to notable improvements in the mechanical properties of the alloys. Surprisingly, both the tensile strength of the alloys and their elongation (and consequently the fracture toughness) were improved by 10-20%. Depending on the nano-structure type and concentration, the hardness, yielding strength, ultimate tensile strength, and ductility were improved by up to ~70%. Physical considerations suggest that the main mechanism responsible for the reinforcement effect lies in the mismatch between the thermal expansion coefficients of the metal and the nano-structures.

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  • Prof. Reshef Tenne
1796
Oil is an important commodity in the global economy, used in numerous industries such as energy, cosmetics, food, personal care, and many more. However, oil based on petroleum is problematic due to finite supply, increasing environmental concerns, and regulations. Oils derived (?) from plant sources...

Oil is an important commodity in the global economy, used in numerous industries such as energy, cosmetics, food, personal care, and many more. However, oil based on petroleum is problematic due to finite supply, increasing environmental concerns, and regulations. Oils derived (?) from plant sources tend to compete with valuable arable land and consume fresh water.

Therefore oil sourced from algae as an alternative is an attractive option, as algae does not pollute, does not require arable land, and can use sea water. Yet current methods of producing oil from algae have limited net yields.

The present technology uses the virus EhV201 to modify the metabolism of microalgae Emiliania huxleyi to increase the production of high quality saturated and mono-unsaturated Triacylglycerides (TAGs). The method is simple to apply in increasing TAG content, does not perturb biomass production, and can even simplify the harvesting of the microalgae produced TAGs.

Applications


·         Directed production of Algal Oil from saturated and mono-unsaturated triacylglycerides for the production of high value products in the food, energy, cosmetics, and pharmaceutical industries.

·         Secondary and tertiary products can be co-extracted or generated from the TAGs and microalgae for different industrial uses:

o   Glycerol and fatty acids for food and cosmetics.

o   Algal cake (residual microalgae material) for animal feed, fertilizers, and so on.


Advantages


?  Straightforward procedure

?  High yield

?  No Genetic Modification

?  Simple and economical - no special equipment or conditions to induce TAG production

?  Scalable- as the EhV201 regenerates itself


Technology's Essence


The application of infecting E. huxleyi with EhV201, to increase triacylglyceride (TAG) production represents a promising innovation in creating an alternative source of oil. The system is simple to apply requiring minimal modification of current microalgae bioreactors. The use of the EhV201 to induce TAG production has been shown to be superior to current established methods of nutrient deprivation. Moreover, the technique does not require genetic modification of microalgae, avoiding regulatory challenges. Finally the technology also has added value being environmentally friendly, and possibly opening the avenue for claiming carbon credits, due to the carbon fixation of the microalgae.

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  • Ph.D. Assaf Vardi
  • Ph.D. Assaf Vardi
1736
Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production. Improvement in the...

Biomass production by plants and other photosynthetic organisms involves carbon fixation, the process of incorporating inorganic carbon dioxide into organic compounds. Currently carbon fixation by plants and other photosynthetic organisms is the limiting factor in biomass production.

Improvement in the metabolic pathway related to carbon fixation would have great value in increasing crop yields, synthesizing high value compounds in algae, and developing means in removing CO2 from the atmosphere to combat climate change.

The present technology is an engineered E. coli with a carbon fixation pathway. The unique innovation can be used to efficiently screen the activity of RuBisCO, the most abundant carbon fixing enzyme on earth, which is further applicable to improving biomass production in different photosynthetic organisms such as plants and algae.

Applications


·      Powerful platform for screening and improving various enzymes in the carbon fixation process.

·      Unique metabolic pathway for use in Synthetic Biology applications.

·      Possible Carbon Credits for developing improved means of carbon fixation.


Advantages


·      E. coli is fast growing and easily manipulated by various genetic tools.

·      Novel source of biomass production.

·      Potentially low cost R&D system.


Technology's Essence


The technology functions by the recombinant insertion of two enzymes from the Calvin-Benson-Bassham (CBB) into E. coli, kinase prk and the carboxylating enzyme RuBisCO. With further modifications, the engineered E. coli’s metabolism was divided into two subsections. First a carbon fixing metabolism that can incorporate inorganic CO2 into sugar production, the second subsection consumes organic pyruvate to produce energy to drive the aforementioned carbon fixing cycle. Subsequently the technology is overall carbon neutral, but is an inexpensive and fast platform for screening improvements in the CBB carbon fixation pathway.

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  • Prof. Ron Milo
1786
Perovskites are a class of crystalline materials with a common complex chemical structure. Lead-halide hybrid organic-inorganic perovskites have recently emerged as highly efficient optoelectronic materials. Such materials are being intensively investigated and developed for photovoltaics,...

Perovskites are a class of crystalline materials with a common complex chemical structure. Lead-halide hybrid organic-inorganic perovskites have recently emerged as highly efficient optoelectronic materials. Such materials are being intensively investigated and developed for photovoltaics, photodetection, light-emitting diodes, and laser devices. Solar cells containing hybrid organic-inorganic perovskites have achieved over 20% certified efficiency.

Perovskites are most commonly synthesized by combining a metal salt (for example, a lead-based salt such as lead iodide) with an organic halide salt in a single step, by spin-coating from a solution of both salts, by co-evaporation, or by a two-step method of forming the metal salt film and subsequently exposing it to the organic halide. The existing fabrication methods suffer from high toxicity, complexity and high energy input.

We present a new method for the preparation of halide perovskites on a substrate for optoelectronic devices and solar cells, including tandem cells that produce higher voltages.

Applications


·      Solar cells

·      Other optoelectronic devices (e.g., photodetectors, light-emitting diodes, lasers)


Advantages


·      Reduced toxicity

·      Simple and straight-forward fabrication method

·      Excellent morphology control of the perovskites


Technology's Essence


Perovskites are crystalline materials with the formula ABX3, in which A and B are cations and X represents an anion. In hybrid organic–inorganic perovskites (HOIPs), A is an organic cation, B is a metal cation, and X is a halide anion.

The synthesis of HOIPs usually involves the use of toxic metal salts (for example, lead iodide or lead acetate) and organic solvents (such as dimethylformamide). Additionally, the combination of a metal salt with several organic solvents, such as dimethylsulfoxide, increases the toxicity of the solution in use.

The new fabrication method utilizes a metal or a metal alloy and an organic halide salt. In the first step, a layer comprising one of the components is deposited on a substrate. Then, the deposited layer is treated with a solution or a vapor of the second component to form a halide HOIP on a solid surface. This method provides a direct conversion of an elemental metal or a metal alloy to a halide perovskite or a perovskite related material. The main advantage of the presented method is the reduced toxicity of the solution used in the process. Additionally, the metals (mainly lead) are much less toxic in terms of manufacturing than the salts of the same metals.

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  • Prof. David Cahen
1798
The rising demand for exclusive visual impact in many applications, along with escalating regulatory requirements drive the development of new, environmentally benign, pearlescent materials. Guanine, a common naturally mineralized material, is being used in a variety of products in industries, such as...

The rising demand for exclusive visual impact in many applications, along with escalating regulatory requirements drive the development of new, environmentally benign, pearlescent materials. Guanine, a common naturally mineralized material, is being used in a variety of products in industries, such as cosmetics, paints and jewelry due to its pearlescence effect. However, the industrial application of guanine crystals is limited since they are extracted from biological sources (mostly fish scales) with limited control over crystals dimensions, morphology and quantity for industrial applications. The main reasons impeding the use of synthetic guanine crystals are guanine insolubility in most solvents and the difficulty of obtaining crystals in the desired morphology. For these reasons, there is a thriving need for the development of a synthetic approach for the formation of well-defined anhydrous guanine crystals with tailor-made properties.

The new technology provides a novel synthetic method for the preparation of highly versatile pearlescent materials, based on guanine crystals, from aqueous solutions. The controllable size and shape of the resulting materials and the sustainability of the method make them suitable alternatives for the existing naturally occurring pearlescent pigments.

Applications


·      Cost-effective and environmentally-friendly approach

·      Control over crystals properties, including size and phase (anhydrous guanine and guanine monohydrate)

·      The same technology can be applied for the crystallization of other materials (purines and pteridines)


Advantages


·      Cosmetics and personal care products

·      Printing inks and decorative paints

·      Automotive paints.


Technology's Essence


Guanine is practically insoluble in neutral aqueous solutions. However, in aqueous acidic or basic solutions, where the molecules are ionized, guanine is much more soluble. The process involves dissolving guanine powder in either acidic or basic solutions, using HCl or NaOH, respectively, and then inducing crystallization by adjusting the pH of the solution. The crystal morphologies differ significantly when carrying out the crystallization in solutions adjusted to different pH regimes. Using pH induced crystallization, the interplay between the initial guanine concentration and the rate of pH change allow substantial control over the crystallization process and ultimately over the crystal size.

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  • Prof. Lia Addadi
1795
Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small,...

Ultra-thin endoscopes are highly desirable for many applications involving remote imaging. Current ultra-thin endoscopes are primarily video-endoscopes and have a shaft diameter of 6 mm or less. Fiberscopes, on the other hand, can reach a micro-meter diameter, thus allowing examination of small, difficult-to-reach, spaces for medical and other applications. Multimode fibers are being explored as ultra-thin lensless replacements for the commonly used endoscopes. The difficulty with imaging or focusing light through a multimode fiber is phase randomization of light propagating through the fiber, which results in a complex speckle pattern at the fiber output. To overcome this obstacle, an access to both fiber ends is required for pre-calibration.

A novel endoscopic method that was developed by Prof. Silberberg at the Weizmann Institute of Science allows light focusing through a multimode fiber by approaching solely the proximal end and retrieving information about the distal end using non-linear optical feedback.

Applications


·         Clinical imaging of narrow cavities (blood vessels, respiratory system, joints, etc.)

·         Selective targeting and burning of fluorescent targets (imaging and treatment)  


Advantages


  • Ultra-thin (micro-meter scale) and flexible

  • Lensless endoscopy

  • High resolution and accuracy


Technology's Essence


We consider a two-photon lensless multimode fiber-based endoscope, where an ultrashort pulse is delivered to a fluorescently tagged sample through the fiber. The pulses excite two photon fluorescence (2PF) from a 2PF screen placed against the fiber distal end. The back-propagated 2PF that is collected by the same fiber is separated from the excitation light at the proximal end by a dichroic mirror (DM), and the Fourier-transformed image of the fiber facet is recorded by an EMCCD camera. It is then used as feedback for a wavefront-shaping optimization algorithm, controlling a spatial light modulator (SLM) at the proximal fiber end. The nature of the light propagation in the fiber allows for scanning and controlling the focus position at the fiber distal end.

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  • Prof. Yaron Silberberg
1679
A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combinationBreast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect...

A novel therapy for Triple Negative Breast Cancer (TNBC) using mAbs combination
Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) representing about 15% of all breast cancer cases, is the deadliest form of all breast cancer subtypes, and tends to affect women at a younger age. Unfortunately TNBC cannot be treated with the common receptor targeted therapies since it does not express these targets, the estrogen, progesterone and Her2/neu receptors. Therefor systemic treatment options are currently limited to cytotoxic chemotherapy. The lack of effective targeted therapies, resistance to chemotherapy, and early metastatic spread have contributed to the poor prognoses and outcomes associated with TNBC.
The current technology offers a novel therapeutic strategy for TNBC. The application of two novel, noncompetitive antibodies against EGFR, achieves a robust degradation EGFR resulting in tumor inhibition.

Applications


  • Novel and unique antibody targeted therapy for TNBC.
  • The novel anti EGFR antibodies can cooperate synergistically with the currently marketed EGFR antibodies.

Advantages


  • A promising therapeutic scenario to treat TNBC.
  • Enhanced EGFR degradation and improved anti-tumor activity, in contrast to clinically approved anti-EGFR mAbs, which display no cooperative effects.
  • Lysosomal EGFR degradation pathway induced by epitope-distinct antibody mixture may potentially lead to improved therapeutic outcome, and reduced resistance.

Technology's Essence


Prof. Yosef Yarden and his team demonstrated that a combination of novel antibodies that target distinct regions on the human EGF receptor resulted in its robust and synergistic down-regulation, leading to pronounced tumor growth inhibition. Furthermore, the combined mAbs induced lysosomal degradation of EGFR, while avoiding the recycling route. Such irreversible mode of EGFR degradation may potentially increase response rate or delay the onset of patient resistance.
Conversely, combining cetuximab and panitumumab, the mAbs routinely used to treat colorectal cancer patients, did not improve receptor degradation because they are both attracted to the same epitope on EGFR.

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  • Prof. Yosef Yarden
1772
MTCH2 as a novel target for the treatment of obesity.Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-...

MTCH2 as a novel target for the treatment of obesity.
Obesity is an escalating public health problem with an increasing prevalence worldwide, and a primary contingency of many life-threatening diseases, as well as early mortality. In the U.S. alone, more than one-third of adults are obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer, some of the leading causes of preventable death. Physicians and patients alike consider the weight-loss efficacy of the current therapeutics to be unsatisfactory. Therefore, there is an unmet need for innovative options that are at once safe and efficacious, and allow the patient to maintain weight loss.
The present invention describes the identification of Mitochondrial Carrier Homolog 2 (MTCH2) as a novel player in muscle metabolism and the therapeutic potential of inhibiting MTCH2 for the treatment of diet-induced obesity and diabetes.

Advantages


  • A fresh approach for targeting weight-related disorders
  • Direct effect on metabolism instead of indirect mechanisms of current therapeutics which target appetite modulation.
  • Protection from diet-induced obesity can be used as a prevention treatment for people with a tendency for weight gain.  

Technology's Essence


MTCH2 functions as a receptor-like protein for the pro-apoptotic BID protein in the mitochondria.
MTCH2 was identified as one of six new gene loci associated with Body Mass Index (BMI) and obesity in humans suggesting that MTCH2 may also play a role in metabolism.
MTCH2 was recently shown by the Gross’s lab to also function as a repressor of   mitochondria oxidative phosphorylation (OXPHOS) in the hematopoietic system.
Deletion of MTCH2 in skeletal muscle increases mitochondrial OXPHOS and mass, and increases capacity for endurance exercise. In addition, loss of MTCH2 increases mitochondria and glycolytic flux in muscles as measured by monitoring pyruvate and lactate levels.
MTCH2 knockout mice are protected from diet-induced obesity, hyperinsulinemia, and are more prone to weight loss upon caloric restriction.
Therefore, the association of MTCH2 with mitochondrial function offers a potential novel target for muscle metabolism modulation in the fight against metabolic disorders such as obesity and diabetes.

 

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1715
Preparation of Re-doped inorganic MoS2 nanoparticles with good sodium ion reversible intercalation properties, to be used as cathode material for next generation sodium ion batteries. Lithium ion batteries (LIB) are currently the leading energy storage solution used in many applications. But lithium is...

Preparation of Re-doped inorganic MoS2 nanoparticles with good sodium ion reversible intercalation properties, to be used as cathode material for next generation sodium ion batteries.
Lithium ion batteries (LIB) are currently the leading energy storage solution used in many applications. But lithium is both toxic and limited in quantity (hence expensive) and cannot supply the growing demand for energy storage units as well as the need for cleaner and safer technologies.
Sodium ion batteries (SIB) are attractive new generation batteries as they incorporate the much less toxic and much more abundant sodium ion.
Our novel nanoparticles were shown to have competitive electrochemical performances with specific capacity of about 130 mAh/g at 2C and 74 mAh/g at high discharge rate of 20C.

Applications


  • Electrode material for sodium ion batteries
  • Possible applications in magnesium ion batteries

Advantages


  • Competitive specific capacity
  • Improved electrical conductivity towards Na ions

Technology's Essence


The cathode material's reversible intercalation capacity plays a significant role in determining the total capacity of an energy cell. Intercalation requires entering of ions into the electrode material through diffusion channels.
The faceted structure of inorganic nanoparticles (IF) induces intrinsic dislocations and stacking faults which serve as ion diffusion channels. Doping of the nanoparticles increases both conductivity, due to n-type doping of the Mo metal, and the number of structural defects (hence diffusion channels), resulting in total increased electrical conductivity.
The synthetic procedure for producing Re-doped MoS2 nanoparticles is straightforward, based on known and published protocols.

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  • Prof. Reshef Tenne
1749
Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity. Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is...

Our novel technology provides an inexpensive, safe and clean solution for loading and unloading of hydrogen on demand with high potential hydrogen storage capacity.
Hydrogen storage is currently the key hurdle to its utilization as an alternative green fuel. Being the smallest molecule, hydrogen is highly diffusive and buoyant. Currently, hydrogen is stored physically as a gas, requiring high-pressure tanks, or in liquid form at cryogenic temperatures, both methods require high energy input. Proposed chemical storage systems are based on relatively expensive materials, suffer from poor regeneration after hydrogen release and require elevated temperatures and pressures.
The presented technology utilizes inexpensive and abundant organic compounds that generate hydrogen gas during a chemical transformation. Hydrogen release and the regeneration of the original compound are performed in mild conditions using the same catalyst. This system is a promising candidate to be the basis of compact and cost-effective chemical hydrogen storage platforms.

Applications


  • High potential hydrogen storage capacity (6.6 wt%)
  • Inexpensive and readily available hydrogen carriers (aminoalcohols)
  • Relatively mild release and regeneration conditions

  • Advantages


    • Hydrogen-fueled systems, including fuel cells
    • High capacity hydrogen storage systems

    Technology's Essence


    The technology is based on aminoalcohols that are catalytically converted to cyclic dipeptides, while forming hydrogen gas, using a ruthenium pincer catalyst. Peptide hydrogenation, using the same catalyst, regenerates the aminoalcohol. The same method can be applied with diaminoalkanes and alcohols as well.
    The reaction requires a relatively low organic solvent volume, a catalytic amount of base (KOtBu) for the in situ generation of the active catalyst and mild reaction conditions in terms of hydrogen pressure (50 bar) and temperature (~100 oC). Repetitive cycles of the dehydrogenation-hydrogenation reactions can be performed without adding new catalyst, while maintaining high percentages of aminoalcohol conversion.

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    • Prof. David Milstein
    1686

    Applications


    • Co-treatment with chemotherapy
    • Co-treatment with statin treatmen

    Advantages


    • Lower collateral toxicities allow for greater flexibility in treatment dosage.
    • Enhanced patient survival rate.
    • More favorably considered as a line of therapy due to decreased side effects.
    • Utilization of well-characterized compounds alleviates safety and toxicity considerations.

    Technology's Essence


    ER stress, elicited by chemotherapeutic agents such as doxorubicin, 5FU, vincristine and bortezomib, or statins such simvastatin, triggers cell death at least in part through generation of leukotriene C4 (LTC4), which induces ROS accumulation, DNA damage and subsequent cell death. LTC4 can be produced by two parallel pathways. Cells of hematopoietic origin express C4 synthase (LTC4S) and secrete their LTC4 load, thereby affecting nearby tissues. In contrast, as discloses by the present invention, non-hematopoietic cells generate LTC4 by the enzyme MGST2 (an isoenzyme of LTC4S), and retain it to act internally leading to their demise. This difference is the basis for the present invention. Thus, LTC4 receptor antagonists (montelukast, pranlukast, etc.) will alleviate the toxicity of chemotherapy towards non-hematopoietic tissues and cells, but retaining the therapeutic effectiveness of chemotherapy on lymphocytic leukemia, lymphoma and myeloma patients. In conjuction, it was found that pranlukast attenuated cell death triggered by a broad range (0.5-4 µg/ml) of simvastatin (a statin) concentrations.

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    • Prof. Menachem Rubinstein
    1782
    L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.Betalains are robust, flavorless, natural water soluble dyes,...

    L-DOPA is a high value compound used in the treatment of Parkinson’s disease and a precursor for other high value compounds. Current industrial methods for producing L-DOPA are problematic in terms of complexity, yield, or toxic byproducts.
    Betalains are robust, flavorless, natural water soluble dyes, in the color ranges of both red-violet and yellow-orange. Currently there is no natural quality source for water soluble natural yellow dyes, with present natural yellow dyes being water insoluble.
    The present technology offers an alternative method that is simple, does not produce side-products, and is non-toxic with Tyrosine being the only feedstock. The technology produces L-DOPA and natural water soluble yellow and red Betalain dyes, both within yeast and in different plant species.

    Applications


    • Production of L-DOPA for use in pharmaceuticals or dietary supplements.
    • Synthesis of water soluble yellow and red natural dyes for use as colorants, antioxidants, and food supplements.
    • Altering coloration of ornamental plants by inserting the metabolic pathway.

    Advantages


    • One-step reaction for L-DOPA synthesis from Tyrosine.
    • Non-toxic and non-hazardous synthesis.
    • Ecologically friendly - no waste management issues.
    • Multiple colors can be produced with yellow, red, or orange if pathways combined.
    • Flavorless - avoid influencing the taste of different products.
    • Flexibility in biosynthetic production - multiple possible host systems.
    • Specificity - no side products produced
    • Mild Conditions - enzyme(s) requires ambient temperatures.

    Technology's Essence


    The present technology takes advantage of the Betalain biosynthetic pathway to selectively produce L-DOPA and natural Betalain dyes. A newly discovered, specific, cytochrome P450-CYP76AD6 begins the pathway, with the capacity to convert Tyrosine to L-DOPA. Then L-DOPA is converted to Betalamic acid via DOPA 4, 5-dioxygenase.
    With the Betalamic acid intermediate, the biosynthetic pathway diverges to make either Betaxanthins (yellow dyes) or Betacyanins (red dyes). In the production of yellow dyes an amine (e.g. amino acid) spontaneously reacts with Betalamic acid. In the case of red dyes, cycloDOPA (generated by the enzyme CYP76AD1 modifying Tyrosine and L-DOPA) and a Betalain-related glucosyltransferase react with Betalamic acid. Furthermore the two pathways can be done in parallel to produce an orange color.

     

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    • Prof. Asaph Aharoni
    1751
    Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets. The present...

    Many cancer cells hijack and remodel existing metabolic pathways for their benefit. Specific targeting of these metabolic dependencies offers cancer patients increased efficiency and minimized side effects. Yet, the complexity of these pathways hinders the identification of targets.
    The present discovery elucidates the pathway by which argininosuccinate synthase (ASS1) down-regulation confer cancer progression. It shows that decreased activity of ASS1 in cancers supports proliferation by linking excess aspartate to pyrimidines synthesis. Importantly, these studies highlight Citrin (a mitochondrial aspartate transporter) inhibition as a potential method to decrease aspartate levels and selectively target this metabolic pathway in ASS1 depleted cancers.

    Applications


    • Targeted Treatment for ASS1 depleted cancers.

    Advantages


    • Targeted therapy, against a well defined pathway, increases the prospects for success.
    • Selective – targeting cancer metabolic dependency minimizes the chances for healthy cells damage that lead to side effects.

    Technology's Essence


    Cancer cells hijack and remodel existing metabolic pathways for their benefit in what is termed the Warburg effect. Researchers from Dr. Ayelet Erez's lab, at the Weizmann institute of Science, have delineated the metabolic benefit(s) conferred by loss of ASS1 to cancers. In agreement with previous experience, they found that ASS1 deficiency has an additional arginine- independent effect that is directly related to its substrate, aspartate.
    By focusing on the relevant physiological and pathological model systems, it was found that ASS1 deficiency-mediated increase in aspartate levels lead to excessive proliferation through pyrimidine synthesis. The link between the two is provided by CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, dihydroorotase complex) and the mTOR signaling pathway.
    Importantly, the present inventors have found that blocking Citrin, the mitochondrial aspartate transporter, rescues cell proliferation by reducing aspartate levels. Citrin may thus serve as a strong candidate for targeted therapy of ASS1 depleted cancers.   
    Supporting this model, retrospective survival analysis of several cancers reveal that cancers with both decreased ASS1 expression and high Citrin levels have a trend for significantly worse prognosis.

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    • Dr. Ayelet Erez
    1665
    Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes....

    Improved magnetic resonance imaging (MRI) for cardiac fibrosis and other fibrotic diseases.
    Myocardial fibrosis is associated with worsening ventricular systolic function, abnormal cardiac remodeling, and increased ventricular stiffness, significantly increasing the risk of adverse cardiac outcomes. Hypertension and diabetes elicit fibrotic processes in the heart, placing a high percentage of the western world population at risk, yet the early identification of fibrotic development in high-risk patients is hindered by lack of adequate fibrosis imaging modalities. This in turn leads to increased morbidity and additional financial burden to health care services. The current standard method to assess myocardial fibrosis employs the usage of MRI coupled with intravenous infusion of Gadolinium contrast agent. However, this method suffers from considerable drawbacks including reduced sensitivity (that permits diagnosis only at advanced stages of disease), lengthy scan times and toxicity of the contrast agent, which excludes a significant subset of patient populations from diagnosis. Thus, the capacity to diagnose myocardial fibrosis in its early stages would allow successful therapeutic intervention, and may also create a platform for the non-invasive study of fibrotic development, thereby facilitating the design of targeted therapies. The current invention is comprised of a novel cardiovascular magnetic resonance method with enhanced sensitivity, without the need for contrast agent administration.

    Applications


    • Detection of cardiac fibrosis due to various pathologies, including hypertension, diabetes and heart failure.
    • The method can be applied to detect fibrotic tissues in a broad range of disorders including cancer, renal fibrosis and pathologies related to skeletal muscles.
    • A platform for the clinical study of targeted therapies that may prevent or arrest fibrotic diseases.
    • Monitoring the efficacy of treatment tailored to target fibrotic tissue development.

     


    Advantages


    • The method relies on magnetization transfer to provide contrast, and therefore obviates the need for any extrinsic, toxic contrast agent such as Gadolinium.
    • Improved sensitivity over current contrast agent-based cardiac MRI methods.
    • The method can be readily applied to existing MRI clinical imaging systems.

    Technology's Essence


    A team of researchers at the Weizmann Institute has developed a novel approach for detection of myocardial fibrosis using magnetization transfer contrast (MCT) MRI cardiac imaging technology. The method was tested in vivo on animal models of heart failure and proved highly sensitive for detection of scar tissue formation and monitoring of fibrotic development. One prominent advantage of the present technology over current cardiac imaging modalities is that it eliminates the requirement for extrinsic contrast agents, thereby circumventing potential adverse toxic side effects.

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    • Prof. Michal Neeman

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