The Synthetic Biology Laboratory for the Decipherment of Genomic Codes
Asst. Prof. Roee Amit http://roee-amit.technion.ac.il/Roee-Amit
Our research combines synthetic biology with advanced imaging techniques to study problems associated with information transfer at the molecular level in biology. Our research efforts are aimed at two major fields:
1. Synthetic enhancer circuits – Deciphering the regulatory code is one of the great challenges of our time. Our approach is to “hack” this algorithm using the tools of synthetic biology. We do this by designing novel DNA regulatory sequences using characterized components, and testing if our “program” displays the predicted regulatory response. At present, this translates to constructing synthetic enhancer elements from the ground up in bacteria, and coupling them to gene circuits to generate increasingly complex modules. In the future, we intend to expand this work to embryos with a long-term goal of developing therapeutic applications.
2. Live tracking of RNA – We approach this problem by utilizing synthetic biology and advanced microscopy methods in order to simultaneously develop a specialized system of genetically encoded fluorescent probes, whose output will be detected by a dedicated imaging system. Our probes will be designed to report interactions of RNA molecules at the single molecule level, and as a result enable quantitative intra-cellular dynamical tracking of RNA and its myriad of biological function and roles.
The Laboratory of Nanostructured Molecular Assemblies
Assoc. Prof. Dganit Danino
Self-organization is a fundamental process dictating the function and properties of many proteins, peptides and lipids. Our studies aim on uncovering the structure, dynamic and characteristics of nanometric complexes which form by this self-organization. Few studies have potential application in food and medicine, as, for example, the design and formation of Cubosomes, nanometric lipid carriers loaded with drugs and nutraceuticals. Other investigations explore mechanisms of action protein nano-machines. Examples include Dynamin, which mediates endocytosis, the main pathway for internalization of nutrients into cells, and MxA, an interferoninduced protein displaying antiviral activity against virus like influenza, hepatitis and Thogoto. Using advanced cryogenic electron microscopy techniques we characterize at high-resolution and in great detail the interaction of such proteins with lipids, viruses and other cell components. This information, combined with detailed biochemical analysis will possibly reveal new therapeutic approaches against life-threatening pathogens.
The Laboratory of Molecular and Applied Biocatalysis
Assoc. Prof. Ayelet Fishman http://afish.technion.ac.il
Biocatalysis is the use of enzymes or cells to carry out defined chemical reactions under controlled conditions, in order to convert raw materials into commercially more valuable products. The high selectivity of enzymatic transformations, combined with the mild reaction conditions and the use of inexpensive reagents, represent sound advantages for biocatalysis. Our interdisciplinary research is aimed at developing novel and efficient processes for synthesizing natural food additives and drug intermediates in aqueous and nonaqueous media. In order to render the enzymes more suitable for industrial conditions, we employ a technique called Directed Evolution. This is a novel approach based on the Darwinian algorithm of mutation and selection, which allows to explore and improve enzyme functions by iteratively altering the amino acid sequence and finding the mutant with the desired properties. Projects in the lab include the synthesis of a natural fragrance compound using yeast isolates, producing enantiopure sulfoxides using monooxygenases, and searching for novel enzymatic activities in genomes derived from soil and sea water.
The Laboratory of Applied Genomics & Food Microbiology
Assoc. Prof. Yechezkel Kashi
Our research team in the Faculty of Biotechnology & Food Engineering at the Technion is focused in three major research fields:
1. Environmental microbiology – genomics, pathogenesis, and evolutionary studies of V. vulnificus and V. cholera.
2. Gut microbiome – understanding the role of host’s genetics on microbial composition and host microbial interactions.
3. Biodiversity and genetics of yeasts, Saccharomyces cerevisiae.
These studies combine methodologies of molecular genetics, SSR genotyping, next generation sequencing, bioinformatics and classical microbiology in culture and in animal models.
The laboratory of chemistry of foods and bioactive compounds
Asst. Prof . Uri Lesmes http://lesmesu.net.technion.ac.il/
Improving human health and prevention of diseases through rational design of food and biotechnological formulations require comprehensive understanding and control over complex chemical reactions and interactions. Our group is involved in studies of complex reactions and interactions of bioactive ingredients using advanced analytical tools and metabolomic approaches. Using unique bioreactors designed to simulate the human digestive tract we also investigate the reactions and events occurring within the digestive tract of humans, throughout the lifespan and across a range of human conditions.
Our ongoing work seeks to harness naturally formed conjugates and molecular hybrids to fabricate novel food-grade ingredients, hydrocolloids, nano-laminated emulsions, modified interfaces, retard contaminant formation and degradation of beneficial components. Through our studies we seek to understand how one can modulate digestion reactions and luminal contents, e.g. reducing lipid digestion as well as personalize nutrition to specific human conditions. Overall, our efforts focus on understanding the potential beneficial and deleterious effects on human health and well-being that originate from man-made manipulations and changes in the structure and composition of foods and other formulations.
The Laboratory of Mammalian Cell Technology
Prof. Ben-Zion Levi http://levilab.net.technion.ac.il/
Bone marrow derived hematopoietic stem cells give rise to all blood cell types among which are myeloid cells that constitute an essential arm of innate immunity. This hierarchical cell fate decisions process is orchestrated by key transcription factors. These factors govern and modulate the expression of lineage specific genes. Aberrant expression of these key regulators results in block in the differentiation process and subsequently leads to leukemias. Lineage specific expression is the hallmark of this complex differentiation process, yet the molecular mechanisms that govern this lineage restricted expression are not elucidated. Our research is focused on the molecular mechanisms that govern transcriptional regulation of genes in general and during myeloid cell differentiation in particular. We study a transcription factor termed IRF-8, which is essential for the ability of progenitor cell differentiation toward the monocyte arm of the myeloid cells. We demonstrate that epigenetics modifications are essential for this lineage specific expression. Further, we study gene regulatory network governed by IRF-8 and its role in the differentiation process, the activity of the mature cells and the suppression of leukemias. Our research will allow future drug design to manipulate the immune system and to eliminate cancer cells and invading pathogens.
The Lab of Food Physical Chemistry & Biopolymeric Delivery Systems for Health
Assoc. Prof. Yoav D. Livney http://biopolymeric-nano-carriers-4-health.net.technion.ac.il/
Proteins and polysaccharides are essential components of food and other biological systems. To improve their stability and functionality during technological processes we study the mechanisms of protection conferred to them by low-molecular weight co-solutes like salts and saccharides in aqueous systems, using advanced instrumental techniques combined with modeling and computerized atomistic simulations.
We also harness the binding of small bioactive molecules (nutraceuticals and drugs) to biopolymers, and their co-assembly, to form nanodelivery systems for promoting human health. In designing these nanodelivery systems we draw inspiration from natural delivery systems, like the casein micelle in milk, which evolved to deliver calcium and protein from mother to the baby. The nano-delivery systems we design, for the enrichment of widely consumed staple foods and beverages with nutraceuticals, confer protection to these sensitive compounds against deterioration during processing and shelf-life, without sacrificing desirable sensorial properties, and promote their bioavailability to the body.
To combat cancer we rationally design targeted nanoscopic vehicles for either oral or systemic delivery, loaded with synergistic combinations of drugs, diagnostic-aids and chemosensitizers to overcome drug resistance. These nanoscopic vehicles employ the “Trojan-horse” approach: selective uptake by cancer cells, followed by release of drugs and chemosensitizers to eradicate the cellswhile labeling their location for complementary treatments.
The Laboratory for Cancer Drug Delivery & Tissue Engineering
Assoc.Prof. Marcelle Machluf URL: http://drugcelltherapy.net.technion.ac.il
The research in our laboratory combines material engineering and life sciences towards the development of new delivery platform of cells, proteins and gene for cancer therapy and tissue engineering.
Gene Therapy: Developing non viral vectors for gene delivery such as ultrasound, nano- polymeric particles made of Chitosan and polylactic co-glycolic acid, alginate.
Drug Delivery Systems: Developing nano and micro size particles for the delivery of anti-inflammatory and anti-cancer drugs particularly anti-angiogenic drugs.
Cell Bioencapsulation: Developing cell encapsulation procedure for cell based therapy. These systems are used to immune protect cells that are genetically modified, primary cells and stem cells.
Tissue Engineering: Engineering organ in the laboratory particularly heart, blood vessels and nerve. Developing scaffolds which are based on 3D accellular collagen matrices isolated from large animals. Developing bioreactors for the long term culturing of tissue engineered organs.
HIV/AIDS: Developing complex proteo-polymeric drug delivery systems for targeting and killing HIV infected cells and for the entrapment of free roaming virions in the blood and lymph fluids.
The laboratory of Molecular Nutrition
Asst. Prof . Esther Meyron Holtz
Iron is an essential nutrient for most organisms. Iron deficiency leads to anemia with its many pathologic implications and iron overload leads to complications such as liver cirrhosis, liver cancer and diabetes. Therefore iron uptake and distribution needs to be carefully regulated and this regulation is the focus of our research. The two Iron Regulatory Proteins are responsible for the regulation of cellular iron uptake. In a mouse model lacking the Iron Regulatory Protein 2 iron distribution throughout the body and especially the brain is miss-regulated which leads to anemia and a neurodegenerative disorder that resembles Parkinson disease. We study the role of the iron storage protein ferritin in the pathophysiology of this neuro-degeneration.
Systemic iron distribution is also depending on macrophages, a cell type that plays many roles including in the immune system. These cells eliminate senescent red blood cells and recycle their iron for new hemoglobin synthesis. Characterization of the macrophage response to red blood cell ingestion may lead to strategies to strengthen the immune system in the many disorders where red blood cell half-life is shortened.
The laboratory of Antimicrobial Peptides Investigations (LAPI)
Prof. Amram Mor
The development of new, safe/efficient and economically viable tools for fighting multidrug resistant (MDR) pathogens is of prevalent need. The Mor group has recently reported a novel design of chemical mimics that is founded on lipopeptide-like oligomeric arrangements of acylated cationic building blocks. Initial characterization of lysine-based representatives (termed oligo-acyl-lysyls, OAKs) led to several intriguing findings: (i) The OAK platform can generate small molecules that selectively exert antimicrobial (and anticancer) properties using distinct sequence-specific mechanisms; (ii) Some OAKs can potentiate certain drugs (eg, antibiotics), restoring sensitivity of MDR cells, in some cases) ; (iii) OAKs interaction with phospholipids induce cochleates formation, which can be exploited for efficient co-encapsulation of the synergistic drugs and for co-delivery in systemic treatment of infection. Collectively, these findings argue for the potential of OAKs in providing a comprehensive system for fighting MDR bacteria.
The group’s current efforts attempt to extend these studies and exploit accumulated knowledge for further developing the OAK approach while focusing on particularly short antibacterial sequences. Thus, design principles that emerged from previous studies are used to inspire the design of new improved derivatives towards defining essential chemo-physical properties that impact extra- and intra-cellular targets, in presence and absence of antibiotics, in-vitro and in-vivo. Knowledge gained over the course of this project will aid in the rational design of optimal antimicrobial agents for mono- and/or combination-therapy.
The Laboratory of Functional Nanomaterials, Biosensors, and Sensors
Asst. Prof. Ester Segal http://segallab.technion.ac.il
Our multidisciplinary research group combines materials science and engineering, biotechnology, and applied physics and chemistry toward the development of novel functional nanomaterials. We design, synthesize and study new nanomaterials for various advanced technologies, including intelligent packaging, sensors, and biosensors. Current and future needs for food quality assurance, food safety and bio-security strongly require new and improved diagnostics to screen for chemicals, toxins and bacterial pathogens in complex food matrices. Introduction of these diagnostic functionalities into food packaging represents the emerging concept of intelligent packaging. Thus, our aim is to develop rapid, accurate, cost effective, reliable, non-invasive and non-destructive sensing platforms that could in future power intelligent forms of food packaging. These materials will be designed to perform different tasks, including detecting, sensing, biosensing, and tagging. We study the interrelation between structure, properties and functionality of our nanomaterials. The potential of these technologies is far reaching, and is expected to have an impact on numerous disciplines including, packaging science, biotechnology, polymer science, nanotechnology, biodefence and sensor science.
The Laboratory of Functional Foods, Nutraceuticals, and Food Nanoscience
Assoc.Prof. Eyal Shimoni. http://www.technion.ac.il/~eshimoni/
Our philosophy is that the efficient manufacturing and use of functional foods and Nutraceuticals requires a comprehensive approach that extends beyond an analysis of the beneficial biological activity. This approach incorporates all stages of the development and manufacturing: the rational design of the ingredients based on an understanding of the relationship between structure and function, the stability of bioactive compounds during processing and storage, development of delivery systems for bioactives, the physico-chemical properties of tailored foods, and the development of innovative technologies for nutritionally enhanced foods. Our research has made advances in each of these areas. The study of material properties at the nanoscale is one of the most exciting frontiers in science. This research group was among the first to become active in food nanosciences and nanotechnology. Our work is driven by nanoscale analytical techniques that enable us to obtain a better understanding of the relationships between molecular structure and macroscopic properties. These concepts have been applied to micro and nano- encapsulation of bioactives in food grade materials.
The Protein and Enzyme Engineering Laboratory
Prof. Yuval Shoham
The natural degradation of plant cell wall matter in Nature is a key element in the Carbon cycle on Earth. Moreover, lignocellulose is considered the most viable option as a renewable energy source that contributes zero net emission of carbon dioxide. The main difficulty in using cellulose as an energy source is its crystalline nature which is highly resistance to hydrolysis. Our laboratory is trying to reveal and understand how enzymes and microbial systems breakdown the plant cell wall material in Nature, and how can we utilize these systems for biotechnological applications. For example, developing an economic process for generating biofuel from cellulose. Our main research systems include the cellulosome complex from C. thermocellum and the hemicellulolytic system of G. stearothermophilus. We utilize an integrated research approach combining biochemistry, X-ray crystallography, genetic engineering, gene-regulation, microbial physiology and fermentation technology. Studies from our laboratory provided an industrial process for the bio-bleaching of paper pulp, and revealed new crystal structures and new catalytic mechanisms of several glycoside hydrolases.
The Laboratory of Molecular Biology of Pathogens
Assoc.Prof. Sima Yaron
Extensive use of antimicrobials for medical reasons and in farms and households has led to the rapid development of resistance in disease-causing microorganisms. Our research efforts are aimed at two major fields: (i) to investigate mechanisms of resistance to antibacterial agents and (ii) to design and develop new antimicrobials to combat resistant pathogens. We particularly study food borne pathogens associated with highly protected states of existence. The research has made advances in each of the following points, and thus has important implications for both combating infections and for food safety.
Microbial resistance: characterization of emerging multiple antibiotic resistant food borne pathogens, understanding the mechanisms of cross resistance to antibiotics, food preservatives and sanitizing agents, and development of new antimicrobial agents to combat resistant pathogens.
Microbial biofilms: biofilm development on different surfaces, resistance of biofilm cells to antimicrobials, and development of new technologies for removal of bacterial biofilms.
Food safety: molecular study of the behavior of food-borne pathogens in water and fresh ready to eat foods.
