the secrets of life

the Lokey Center ReportTechnion - Israel Institute of Technology

the secretsof life

A publication of the Lokey Center. May 2012.for further information, please see http://lokey.technion.ac.il

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“It is not the strongest of the species that survives, nor the most intelligent that survives. It is the one that is the most adaptable to change.”- Charles Darwin

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The Lokey Center Report 2012

“Convergence is... an exchange of mindsets and a result of true intellectual cross-pollination.”

Prof. Yuval Shoham, Director

Welcome to the 2012 report of the Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering (LS&E). The foundational vision of the Center was conceptualized in 2006 by Nobel Laureate, Distinguished Professor Aaron Ciechanover, together with the visionary philanthropists, Mr. Lorry I. Lokey, and the Technion’s management. The Center’s main vision was to merge the renowned capacity of the Technion’s engineering faculties with life science and medicine.

Recently, a white paper formulated at MIT suggested that the life sciences are entering a third revolution. Twenty years ago, we were in the midst of the molecular biology revolution, which allowed us to isolate single genes, express them, study their properties, and introduce specific mutations into living cells. Less than ten years ago, the genomic revolution began – with the development of parallel sequencing technologies and the completion of the human genome. This revolution was accompanied by new fields of “omics” research, including metagenomics, proteomics, metabolomics and more. We are now entering the third revolution of life sciences, coined the “convergence revolution,” with the confluence of life sciences, the physical sciences, and engineering. Convergence is more than simply joining experts in two or more disciplines to swap ideas; it is an exchange of mindsets and a result of true intellectual cross-pollination. Convergence also carries consequences for the structure of university science departments, funding, and how the next generation of scientific researchers and engineers will be educated. The Technion is in an excellent position to ride the wave of this third revolution, due to its superb engineering faculties; the unmatched quantitative skills that our students acquire during their studies; and its built-in medical school. This convergence revolution requires us to re-educate ourselves and change the academic research culture in order

to cross the barriers between classical disciplines formulated many years ago. The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering initiates, inspires and fosters horizontal integration of different scientific fields by lowering the traditional barriers between the classical disciplines. After the vision, comes the implementation: with the erection of the beautiful Emerson Family Building for Life Sciences – which is a major focal point of LS&E activity, many of the infrastructure units have found their home. The building is hosting today state-of-the-art support units, including genomics, proteomics, microscopy, and cell sorting. Very soon we are expecting to complete the Structural Biology Center on the ground floor. Together with the Russell Berrie Nanotechnology Institute under the leadership of Prof. Yeshayahu (Ishi) Talmon we are now conceptualizing the NanoMed Initiative in which bio- and nanotechnology will be merged for developing nano-scale solutions for the benefit of humankind. For Israel, LS&E represents the birth of a new form of life science. Our facilities are among the most advanced found anywhere in the world; the multidisciplinary members of our staff are each pioneering unique fields. The depth of commitment and pride in this new Technion venture into the life science of tomorrow are contagious, and I am convinced that this endeavor is going to bring outstanding results in the future. Together, step by step, we are beginning to unravel the mysteries of physical life.

Prof. Yuval Shoham, Director, Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering

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“At Technion, we found the way to stay alive was to perpetually think ahead...” - Prof. Peretz Lavie

In the last decade the Technion has embarked on a new road in science aiming at removing the barriers between fields in science and encouraging interdisciplinary collaborations. One of these endeavors was in marrying life Sciences and Engineering. This was a formidable task, building an environment that will allow researchers coming from such different backgrounds to collaborate and flourish together. Nobel Laureate in Chemistry Aaron Ciechanover stood up to the challenge! He was convinced that to facilitate science, technology and engineering of tomorrow, we need to create new, powerful structures for multidisciplinary research. Our Nobel Laureate sought to do that for Life Sciences, and we were blessed by the support of a man of exceptional vision and generosity: Lorry I. Lokey. I vividly remember our first meeting with Lorry, when distinguished Prof. Ciechanover presented the Technion vision of bringing together engineers and life scientists, explaining why this interdisciplinary approach is the only way to make progress in science. Lorry attentively listened, smiled and said, “I will do that”... And this was the start of a marvelous journey.

The interdisciplinary road taken by the Technion a decade ago has been quickly adopted by others. In 2011, Technion and Cornell University were awarded the right to establish the Technion Cornell Institute of Innovation (TCII) on Roosevelt Island in New York City. This ‘school of the future’

born to bring advanced research, innovation and technological prowess to New York City is to be organized in structures of multidisciplinary ‘hubs’, an innovation inspired partly by the success of creations such as the Lorry I. Lokey Center for Life Sciences & Engineering at the Technion. One of these hubs will bring together scientists from different disciplines to create innovations for a ‘healthier life.’

In 2012, we celebrate 100 years since the laying of our first cornerstone in 1912. Back then, on the mosquito plagued undeveloped slopes of Mount Carmel, life sciences amounted to literally, ‘staying alive’. At Technion, we found that the way to stay alive was to perpetually think ahead, and to keep our eyes firmly fixed on the horizon of new developments in science, technology and engineering. In this, we found structures for world-class science and unrivaled excellence in teaching, entrepreneurship and innovation. LS&E is a prime example of such a structure in the new millennium.

This spring, a new Technion Nobel Laureate will be planting a tree in Lokey Park. With the support of Lorry Lokey and the continued implementation of his vision for life science in Israel at the Technion, I have no doubt that Prof. Dan Shechtman will be followed by others in the coming decades.

Prof. Peretz Lavie, Technion President

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Serenely reflecting sunlight at the heart of Technion City, connected to the Faculty of Biology via the Trudy and Norman Louis Double-Helix Bridge, the Emerson Family Life Sciences Building is dynamic and yet sedate – a custom-designed, elegant structure that gives form to the dynamic interdisciplinary activity taking place across the spectrum of life sciences and engineering.

spacecreative

Researchers from the Faculties of Biology, Biomedical Engineering, Chemical Engineering, Physics, and Biotechnology and Food Engineering have been

drawn to this live center where the world’s most advanced infrastructure serves as a backdrop for scientific exchange and collaboration.

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Molecular Milestones in DevelopmentSince Aristotle, biologists have looked at the embryo and have seen what appears to be distinct stages, as the embryo proceeds from egg to adult. “The appearance of such stages” says Dr Itai Yanai, “may be an interesting artifact or reflect a real, underlying modularity of development.” A new study from his lab employed genome-scale analyses of temporal and evolutionary changes in developmental gene expression to reveal conserved milestones of stable transcription that punctuate bursts of change and suggest the existence of a molecular phylotypic stage.

Laureate LecturesProf. Venkatraman Ramakrishnan, Nobel Laureate 2009 (Chemistry), Cambridge University, delivered a 2011 lecture entitled: The Structural Basis of Decoding by the Ribosome as part of the Lokey Center Distinguished Lecture Series. The Nobel Laureates planted a tree to celebrate the occasion, in accordance with the tradition of Prof. Albert Einstein, founder of the 1st Technion Society.

A Day in the LifeInternational exchange, multidisciplinary workshops and lectures, scientific debate at impromptu meetings at the espresso machine, a touch of art & culture and a lot of soul... this is another day in the life of the Lorry I. Lokey Center for Life Sciences and Engineering at Technion.

“Our next generation of scientists and Nobel laureates, and the future of the Technion depends on the Lokey Center.” Prof. Ramakrishnan and Prof. Ciechanover

Dr Itai Yanai and Ph.D Student Michal Levin

Catch your BreathTrace organic compounds in our breath contain vital information about the inner workings of our bodies, but they can be difficult to detect. Prof. Hossam Haick and colleagues have described how to identify signs of lung cancer and kidney disease in breath samples using arrays of carbon nanotubes. The patented NaNose developed by Haick is being developed for commercial application worldwide.

Oceans AliveClose to 99 percent of life in the ocean can not be grown in pure culture and therefore many of their secrets remain veiled in the mysterious deep. At the lab of Prof. Oded Beja, field trips to the ocean of the scientific team have illuminated the role of microorganisms in the open seas, bringing dramatic insights to the science of life — for example in the area of photosynthesis and the genes found in the cyanophages. “Photosynthesis is a very important part of global life processes,” explains Beja, “About 50 percent of the planet’s photosynthesis is done by the ocean, and 50 percent of this is done by cyanobacteria.” Beja’s research was published in a recent article in Nature.

Of Science and ArtScientists and visitors from across Israel convened on May 16th this year at the Emerson Family Building for Life Science for the festive opening of the 2012 art exhibition entitled: “The bridge between art and science.” Featuring work by the artist Rinat Kishony, the event included a lecture on Brain, Art & Creativity by Prof. Idan Segev of Hebrew University.

Brain to BrainFrom the microscopic to the macroscopic, brain structures are broadly distributed, heterogeneous, highly variable, and non-stationary. In May 2012, the latest research on this phenomena was discussed at the Variance and Invariance in Brain Behavior seminar at Technion.

Distinguished lecture seriesAs part of the Distinguished Lecture Series in which top world scientists are hosted by LS&E at Technion and lecture on various aspects of life science, notables such as Prof. James Rothman, Prof. Vincenzo Cerundolo, and Prof. Felix Wieland exchanged with faculty and students.

Prof. Hossam Haick, Dr Yoav Broza andIrena Dvorkind

Prof. Peretz Lavie with Israeli artist Rinat Kishony

Distinguished lecturer, Prof. James E. Rothman with former Lokey Center Director and Nobel Laureate, Prof. Aaron Ciechanover

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InfraStructurelife unitThe Life Sciences and Engineering Infrastructure Unit was set up in 2007 as a collaborative venture between LS&E and RBNI (The Russell Berrie Nanotechnology Institute). In five years, its staff has quadrupled and today eight highly-trained technicians offer training and expert services to faculty and industry – operating six microscope systems, three flow cytometers, two real-time PCRs, and the Deep Sequencing genomic facility.

Researchers meet at the infrastructure unit from diverse disciplines across the spectrum – from biology through medicine and biotechnology to physics and computer science. The unit currently serves over 70 research groups from Technion, 20 groups from Israel’s other universities and 10 from Israel’s industrial sector. In the last two

years, more than 50 papers where published with the use of the instrumentation of the Infrastructure Unit. The unit also organizes academic courses, conferences, workshops and symposiums in the fields of Microscopy, Flow Cytometry and Genomics.

At the frontline of technology for the service of researchers in life science and engineering, the infrastructure unit continues to expand. Plans for the coming years include the addition of sophisticated systems, including an automation robotic system for sample preparation for the HiSeq 2000, high throughput microscope and more. It is also scheduling two additional academic courses in the field of biomedical research.

HiSeq2000 > a jewel in the crown of life science infrastructure and the first in Israel – the HiSeq is used for massive parallel sequencing of DNA and RNA molecules.

Light Microscopy >Two confocal scanning microscopes, and three fluorescent microscopes and a high throughput imaging system.

Flow Cytometry >Two instruments serve as analyzers, and one instrument as a sorter of analyzed particles or cells for further research.

Two quantitative real-time polymerase chain reaction Instruments.

A Histology unit.

Genomic and High-Throughput Sequencing (known as Next Generation Sequencing, or Deep Sequencing)

The unit features:

Dr Maayan Duvshani-Eshet, LS&E Infrastructure Unit Head Image of cancer cells using the LSM 700 confocal microscope

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get the sequence

The sequence of DNA encodes the information needed for living things to survive and reproduce. Because of the key nature of DNA to living things, knowledge of DNA sequences can make all the difference in practically all biological research. For example, in medicine it can be used to identify, diagnose and potentially develop treatments for genetic diseases, in particular for personalized medicine treatments. Similarly, research into pathogens may lead to treatments for contagious diseases. Revolutionary tools for DNA and RNA, such as the HiSeq 2000 Illumina are enabling rapid advances in disease research, drug discovery, and the development of molecular tests in the clinic.

know the cells

Light microscopy allows scientists to images tissues, cells and particles in high resolution. Lasers, or fluorescent light is used to excite fluorescently labeled molecules attached to different organelles in the cell. A fluorescence microscope is an optical microscope that uses fluorescence to study properties of cells and particles. Confocal microscopy is used to increase optical resolution and contrast of images by using point laser illumination and a spatial pinhole. It enables the imaging of thicker specimens, like whole tissues, and it enables the reconstruction of three-dimensional structures.

go with the flow

Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical characteristics of up to thousands of particles per second. Flow cytometry is routinely used in the diagnosis of health disorders, especially blood cancers, but has many other applications in both research and clinical practice. A common variation is its use to physically sort particles and cells based on their properties, so as to purify populations of interest, mostly in stem cell research.

a chain reaction

Real-time PCR or polymerase chain reaction is commonly used for both diagnostic and basic research. Diagnostic real-time PCR is applied to rapidly detect nucleic acids that offer diagnosis of infectious diseases, cancer, genetic abnormalities and more.In basic research, real-time PCR is mainly used to provide quantitative measurements of gene transcription. The technology may be used in determining how the genetic expression of a particular gene changes over time, such as the response of tissue and cell cultures to an administration of a pharmacological agent; progression of cell differentiation; and in response to changes in environmental conditions.

Dr Nitsan Dahan Head of Imaging & Microscopy Unit

3D rendering of cells organization in tissue, imaged by the LSM 510 confocal microscope

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The Lokey Center’s Bioinformatics Knowledge Unit (BKU) empowers scientists from Technion and affiliated hospitals by offering sophisticated computational methods and tools to make their research faster, more efficient and more economic. BKU services include consultation with individual labs; the organization of workshops and seminars for students, technical, and academic staff; and the development of customized computing tools and data resources. BKU has hosted over 20 major workshops in bioinformatics, and has been involved in over 120 research projects.

with courtesy the Bioinformatics Knowledge Unit

(l-r) Dr Fabien Glaser, Prof. Yael Mandel-Gutfreund, Dr Michael Shmoish, and Dr Sharona Elgavish

Prof. Yael Mandel-Gutfreund, BKU Director and academic advisor

As the Human Genome Project completes its final stages, Lokey researchers are already immersed in the next frontier of basic science – the Human Immunopeptidome Project. They are proposing the launch of an international research project to define in great details the repertoire of immune peptides presented by human cells and to use these peptide fingerprints to diagnose disease and personalize treatment.

With a wealth of information from the human genome project, researchers at Technion are first into the waters of putting it to use. Prof. Arie. Admon at the Faculty of Biology and his research student Dr. Michal Bassani-Sternberg have revealed a methodology through which a simple blood test can potentially diagnose a range of diseases, including cancer, findings that were published in the prestigious journal, Proceedings of the National Academy of Science

(PNAS) in 2011. The method could also help develop and refine immunotherapies for infectious diseases, cancer and autoimmunity.

The new approach is based on the fact that cells can reveal diverse repertoires of peptides as a way of informing the immune system of the state of health. Peptides presented at the cell surface by the Human Leukocyte Antigen (HLA) protein give an alert of imbalance in health. Analysis of these peptide repertoires, nicknamed ‘the immunopeptidomes’, with advanced tools, facilitates the development of better vaccines for both infectious diseases and cancer. Furthermore, familiarity with these immunopeptidomes provides a rich source of information about the ways cells function and respond to diseases and stimuli.

Admon and Bassani-Sternberg propose that the time is ripe for the launching of this new Human

Immunopeptidome Project, which will focus on the identification of entire repertoires of peptides presented by all the different types of cells, both in health and disease. Since the HLA protein is somewhat different between people (it is the most polymorphic gene among the different human genes with more than 3000 known alleles) and each of its subtypes presents a different set of peptides by the cells, the proposed immunopeptidome project will aim to define the unique characters of peptides presented by each of these subtypes of HLA molecules. Recent developments in mass spectrometry are powerful enough to allow identification of tens of thousands of different peptides.

The innovative blood test for cancer already developed by the team based on this methodology has been patented by T3 - the Technion Office for Technology Transfer.

beyond the genome

Did you know

A protein is one or more polypeptides more than about 50 amino acids long.

An innovative blood-test for cancer is just one of the promises of research at the National Proteomics Center headed by Prof. Arie Admon.

Prof. Arie Admon with Dr Michal Bassani-Sternberg

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TCSB

In its centennial year, 21st century milestone in science will be applied at the Technion with the opening of the new Technion Center for Structural Biology (TCSB) within the Lorry I. Lokey Center for Life Sciences and Engineering (LS&E). The center, headed by Dr Hay Dvir, will offer world-class facilities for macromolecular crystallography unrivalled anywhere in the Middle East – making Technion a magnet for life sciences. “You can understand molecules better when you know what they look like...” says Dvir.

Structural Biology is a branch of biology that focuses on the relationship between the 3D structures of biological macromolecules, such as proteins and DNA, and their biochemical or physiological function. “Since biological macromolecules are too small to diffract visible light

they are ‘invisible’ even with the largest light microscope.

X-ray crystallography is the most powerful methodology for resolving objects at atomic resolution. The chemical properties of biological molecules, as revealed by their X-ray structure, help us learn about their interaction with other biological partners and/or with drugs,” says Dvir.

This is the methodology used by Nobel Laureate Ada Yonath to elucidate the structure of the Ribosome. Now Technion scientists will have 21st century equipment to support their research in-house rather than remotely as done before. When it comes to revolutionizing life sciences through the latest tools of X-ray crystallography, “Seeing is believing”, says Dvir.

The job done by a new state-of-the-art X-ray diffractometer to be housed in the Emerson Family Building for Life Sciences once would have needed a Synchrotron – a giant facility that would demand half the space of Technion City to fulfill its job. “Nowadays, a revolution in brightness allow home-source beams to provide quality comparable to 2nd generation synchrotrons,” says Dr Alian Akram, “This is a huge advancement in what we can do and in the quality of data we can obtain. With the investment of Mr. Lokey, Technion is now taking life sciences in Israel to a whole new league.”

The power behind the new center originates with two new recruits: Dr. Akram Alian and Dr Hay Dvir.

“seeing isbelieving”

Did you know

X-ray crystallography is used to determine the arrangement of atoms within a crystal. A beam of X-rays strikes a crystal which causes it to spread in many specific directions.

“Structural Biology has not existed as a discipline at the Technion. Thanks to Mr. Lokey we are now laying its foundation.” - Dr Hay Dvir

Dr Akram began his career in Agricultural Engineering in the University of Jordan. Driven by a vocation to unveil the mysteries of living cells, his career moved through prize winning medical research at the Medical School of the Hebrew University and groundbreaking research into protein chemistry and biophysics at the University of California in San Francisco, CA. It was the existence of the multidisciplinary Lokey Center and the promising new TCSB which tempted him back to the Technion, he says.

Dvir – a senior crystallographer, began his career as a ‘Summa cum laude’ graduate of the Hebrew University. From his groundbreaking structural studies on two important

enzymes for the treatment of Alzheimer’s and Gaucher disease, he moved to the Salk Institute in California for his postdoctoral studies on integral membrane proteins. Later on as a La Jolla Institute for Allergy and Immunology Research Scientist, his research focused on molecular dysfunctions leading to elevated levels of cholesterol in the blood; a hallmark of cardiovascular diseases, which he continues to investigate here. It was the opportunity of promoting and establishing rigorous Structural Biology research which attracted him to head the TCSB. “Being part of the viable life sciences environment at the Technion,

conducting cutting-edge structural research, educating Technion students with Structural Biology and doing all of this in Israel is about all that I could have wished for career wise,” says Dvir.

Conduct basic biological

research using X-ray Crystallography and complementary biophysical and biochemical tools.

Educate and provide biomedical scientists

with state of the art infrastructure to study biological macromolecules at high resolution.

Partner with investigators

on campus with complementary research efforts to promote broader interdisciplinary scientific programs.

TCSB Mission1 2 3

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It sounds like modern warfare, and indeed, even when aiming to outsmart a killer virus on a scale of about 100 nanometers, the latest technology makes all the difference. One of the deep passions behind Dr Akram Alian’s pioneering crystallographic work at LS&E is a desire to advance treatments for HIV, the causative agent of AIDS.

Scientists in Alian’s lab investigate the general principles of how aggressive virus lock into the genetic resources of a patient – and how to prevent them from doing this. “It is a MUST to learn about

the critical interactions and the mechanisms of resistance,” says Alian. The team is taking a sharp look at pathogen-host interaction and how the HIV virus literally hijacks the machinery of the host cell in order to replicate itself, and how it escapes the immune system. “We are hoping to determine the structures of key interacting molecules and develop new intervening strategies and drugs that prevent their interaction. We also want to understand the mechanism of emergent resistance in the proteins of this virus,” says Alian.

Current drugs for HIV bind viral proteins – and yet it continues to mutate and regenerate. Alian’s team is working on a protein discovered in 2004 – intrinsic immunity APOBEC3G. This protein attacks the genome of HIV and causes hypermutation that leads to an abortive replication cycle for HIV. However, HIV expresses a protein that destroys APOBEC, so the Alian’s group wants to understand this process better so that it can be blocked.

Outsmarting HIV

Did you know

HIV (human immunodeficiency virus) infects cells of the immune system. It remains one of the world’s most significant public health challenges, particularly in low- and middle-income countries.

Dr Akram Alian

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youReadingA revolution in genome sequencing technologies, and their biomedical applications is underway, says Prof. Amit Meller of the Lokey Center. In the near future precise diagnosis and medication will become possible by real-time, genetic analysis of patients’ needs from a device that will be about the size of a desktop printer.

Imagine you walk into the office of your doctor. You have been suffering from heartburn, and are worried, as your uncles both died of heart disease. The doctor takes a sample, and within twenty minutes can give you a genetic read-out – you will know where the worry is, what is needed, which medications will work

and which will be ineffective or with dangerous side effects. You will know if you are at risk or if heartburn just suggests less fried foods. General medicine has undergone a revolution. The above scenario would be just one outcome of the coming revolution in medical diagnostics, says Prof. Amit Meller. The

efficient, fast and highly effective genome sequencing platforms of the future will impact scientific research across the frontiers, creating undreamed of possibilities for the treatments and drug developments of tomorrow. Meller’s company, NobleGen Biosciences is active in producing such tools for the next generation of medical treatment and research. And at Meller’s two labs at the Lokey Center at Technion and at Boston University, the integrated science and engineering teams are developing technologies relevant to the life sciences of tomorrow.

“My hope is that the way disease will be diagnosed in the next decades will be different from what

we have been doing so far,” says Meller. “There is a convergence of multiple technologies involving information processing knowledge on the genomic level and the ability to process a very small number of cells. The biomolecular diagnostic companies are looking towards a transition to tools that rely on ultra-fast genome analyses, to be used in any clinic. We will have the research tools and knowledge to look at a person’s genome and to choose the most efficient drugs. It’s just a matter of bringing those technologies to the diagnostic market.”

One of the key attractions of the Lokey Center, says Meller, is that he saw it would be possible

Prof. Amit Meller

to integrate two sides of himself – and two important strains of life science research – basic

science and applied engineering. As a freshmen student at Tel Aviv University, he remembers, he was unable to choose between physics (how to understand things better) and engineering (how to make things better). Today, as a world-class scientist with active labs both at Technion and Boston University, he knows that both are critical. “We are living in extremely exciting times with respect to how science is done,” says Meller, who has nine patents in life sciences to his name, seven of which are already licensed.

As such, he is handpicking just the right mix of multidisciplinary

scientists for his research group in Israel. “We want to be both useful

and exciting. The combination of basic and applied science makes the experience of research much more enriching and interesting. Students from the biophysics side will always be challenged by the engineers… who know they can do it better. And when an engineer presents a better method – for example, for reading an RNA transcript, the scientist will challenge him with ‘where is the question? Is it worthwhile pursuing?’ I really enjoy this kind of multidisciplinary intellectual interactions – a positive tension – among colleagues in the same group.” Take a look into the lab

complex of Prof. Amit Meller at the Emerson Family Life Sciences Building and breath in the future. An integrated synergy of biology, physics and engineering; a structure set up to support seamless global collaboration; and pioneering multidisciplinary science that is set to revolutionize the medicine of tomorrow. From the shining white infrastructure for biological research, through electric doors to the darkened, silent halls of advanced molecular physics, this top recruit of the Lokey Center signifies the first frontier of pure science and engineering in the third millennium.

“We have something unique to offer.”

“I wanted to focus my impact at the intersection of engineering and life sciences. When I heard about the Lokey Center, I immediately realized that this is something I could profoundly identify with.”

Did you Know?In 2004 the National Human Genome Research Institute (NHGRI) at NIH launched a program for the development of revolutionary genome sequencing technologies – the “$1,000 Genome”. The main objective of this project is to focus on applied research for the development of ultra fast and cheap DNA sequencing technologies. Although the “$1,000 per genome” should only be taken as a figure of merit, it sets a scale for the ultimate goal – between 4 and 6 orders of magnitude cheaper and faster than current state of the art technologies.

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stem cellsBiomaterials

&en-masse

Lokey scientist Prof. Dror Seliktar made headlines with the introduction of patented sophisticated gels to speed up the ability of the body to regenerate after traumatic injury, now undergoing clinical tests in Europe. Now, his research team at the Lokey Center for Biomaterials and Tissue Regeneration is working on a new material for the mass production of stem cells to make their commercial use viable on an industrial scale. “In the biotechnology industries, there is an inherent need for expanding populations of stem cells for therapeutic purposes,” says Seliktar of the Department of Biomedical Engineering, who has published over 50 papers in the field, won over 14 awards and launched one of Israel’s promising biotech startups, Regentis Biomaterials. The team has identified a real practical need for effective handling

of stem cells if they are to be widely used in the future. The culture techniques that are premised on laboratory petri dishes will have to be replaced by larger vessel reactors. A patented customized gel developed by the team provides the substrate needed by stem cells to grow and multiply in these specialized reactors. “Using our material technology, we have the ability to adapt stem cell cultivation into a 3D suspension reactor,” says Seliktar. “We can encapsulate the cells in the gels which sit inside the reactor... allowing the cells to perceive an anchorage dependent environment normally provided by the petri dish culture methods.” Lorry Lokey’s vision in investing in multidisciplinary research into life science and engineering is changing the scientific and industrial horizon in Israel, says Seliktar, whose 12-strong team includes eight PhD

Prof. Dror Seliktar

“Using our material technology, we have the ability to adapt stem cell cultivation into a 3D suspension reactor”

“If you get a traumatic injury to the knee, very few treatment options are available,” says Prof. Dror Seliktar, giving an example of one use of the innovative biodegradable hydrogels being marketed by a company he founded, Regentis Biomaterials. “A replacement knee may eventually be required if the progression of the injury is not contained. If you are injured at age 25, it can be pretty daunting to know that at age 55 you may need a knee replacement. We can alleviate the progressive degeneration with a therapy that actually helps repair the tissue – intervening early on and preventing further

degeneration.” Established in 2004, Regentis Biomaterials is commercializing innovative biodegradable hydrogels for the local repair of damaged cartilage and bone. The platform technology is a family of hydrogels called Gelrin™. These gels can be injected or applied to a specific local site and offer beneficial properties for the local repair of damaged tissue such as cartilage and bone. “The company is pretty unique in Israel, and also in the world,” says Seliktar. The Lokey Technion lab is among only a handful of laboratories worldwide that have developed novel biomaterials that are now clinically applied.

Regentis Ahead

students in disciplines ranging from biotechnology engineering, materials science, chemical engineering, biology and more. “We really benefit from the new facilities and new labs made possible by the generosity of Lokey. My lab is an environment that optimizes the type of research we are doing, both in the context of how students react in an interdisciplinary fashion, but also in providing a work place that is friendly and enabling for the students to be creative and

efficient and diligent. “On a global perspective, it has enabled us to bring in excellent scientists that contribute to the innovation of this place. This has expanded our ability to make an impact on the scientific and clinical worlds.”A keyword with Seliktar is regeneration, and he describes the Lokey foundation gift as having a regenerative impact on the Technion. “These are our next generation of scientists and Nobel Laureates,” he says, “The future of the Technion relies on that.”

Did you know

In biology, regeneration is the process of renewal, restoration, and growth that makes genomes, cells, organs, organisms, and ecosystems resilient to natural fluctuations or events that cause damage. Every species is capable of regeneration, from bacteria to humans.

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An interdisciplinary team, a world-class biological facility and a sound-proof physics lab detached from the whole vibe. This is the world of new recruit Dr Ariel Kaplan, who has created the heart of stillness in the basement of the Emerson Family Building for Life Sciences to minutely examine the mechanisms of single molecular motors and biological molecules.

“We think like physicists but we study biology. It’s a very interdisciplinary approach and that means we need interdisciplinary facilities.”

Dr. Ariel Kaplan

The difference between single-molecule biophysics and classic approaches to study cellular life, says Dr Ariel Kaplan, is like the difference between observing the general movement of a herd of animals, and having the opportunity to look at each one close up, defining gender, age, and the way in which the animal walks, stands, sleeps and feeds.

“We study biological systems, looking at one single biological entity at a time,” explains Kaplan, who was recruited to the Lokey Center in 2011 from the University of California, Berkley. At the Kaplan Lab, mechanical forces in biology are examined with the precision of a physicist – in particular, the function of the nucleic-acids processing machinery. On one side, the lab develops experimental setups that can apply mechanical forces on biological molecules and complexes, directly measuring molecular movements as small as Angstroms. On the other side, they use these instruments to study the machine-like function

of polymerases, helicases and translocases.

“As opposed to the classical biologist or chemist that would have a test tube with millions and millions of copies of the same molecule or protein working - we build systems in which we look at a single molecule or protein,” explains Kaplan, describing the difference between single molecule biophysics and more classic biological approaches to research. “At a football stadium, if you look at the crowd from far away, you are not able to see each individual, but you can see some general properties. You can see people moving; you can know the average color of the hair or of their shirts. But if you want to really study how a person moves or acts, it’s not enough to look from far away at the average properties. If you can look closely, you can see that some of them are women and some men, some are children, and only if you get very close will you be able to see each one separately – see their motion, how they stand, how

they sit, how they interact with each other.”

The basic scientific revelations of the physics of the cell will have implications. “One of the motors we work with, is an enzyme that belongs to the HIV virus,” says Kaplan. “We are using these very technological methods to completely understand the enzyme’s cycle, and all the things it needs to do to take one step. After we understand all these things we want to understand how specific inhibitors (anti HIV drugs) work. If we can understand how this motor works, then others can use this knowledge to develop methods to make it harder for the virus to function. With the support of Lorry Lokey, we have been able to build a lab with the required equipment and build the different set ups… it’s not trivial to cross this gap into the cutting edge of interdisciplinary research, and I think that with the support of the Lokey Center we are doing that.”

(on the move)molecule

“We think like physicists but we study biology. It’s a very interdisciplinary approach and that means we need interdisciplinary facilities.”

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Sebastian Reinartz

Attracted to Technion by the Lokey Center and the pioneering research of Prof. Shimon Marom of the Faculty of Medicine at the Network Biology Research Laboratories, Sebastian Reinartz from Germany is just one of the hundreds of graduate students at Technion immersed in researching various aspects of life science and engineering. Reinartz was attracted by the pioneering pulse of the scientists at the Lokey Center has an ambition to be able

to control a single neuron within a living network, as well as to establish a method for studying the processes in neuronal networks that could underlie learning and memory. “I was attracted by the creative concepts that were published from the group of Prof. Marom, and his open-minded way of dealing with his students,” says Reinartz, “It is always advantageous to break walls.

Some questions, especially when it comes to complicated issues like the brain, can only be solved by combining different scientific fields... There are several international project collaborations, workshops and a multitude of invited speakers, so for me this is a great set-up. Generally speaking, this place of intense multidisciplinary cooperation can stand as a role model for the future of science.”

An Open mind

“The Technion is a beautiful place. I very much appreciate the effort to integrate foreign students. I will leave some excellent colleagues and great friends when I finish my degree, with relations that will hopefully remain my whole lifetime.”

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the Rosetta

All languages are codes that can be cracked by referring to a key text which brings the means to decipher the whole. In synthetic biology, scientists are doing just this – aiming to create the biological Rosetta Stone that will offer the keys to unraveling the human genome. The Lokey Center’s Rosetta Stone, created by Dr Roee Amit and his team, is based on novel gene regulatory circuits in bacteria and zebra fish embryos. “Now we can understand, at least partially, many natural programs that have not yet been decoded by simply reading the DNA sequence,” says Amit, whose findings were published in the prestigious journal Cell. “Now we can understand, at least partially, many natural programs that have not yet been decodedby simply reading the DNA sequence.”

Amit, of the Faculty of Biotechnology and Food Engineering, began his research as part of a post-doctoral fellowship at Caltech. The objective of the Technion team is to decode the “software” thatcontrols the process and use this knowledge to develop medical applications. “One of the central discoveries in biology in the post-genome era is the understanding that the main factors contributing to the differences between organisms (for instance,

between mice and men) is not the result of genes,” he explains. “The origin of this difference is in the algorithm or program that determines when, where and how any gene will be expressed. In the pastfew years a new picture of the genome is becoming clearer, and as a result, also a model in which the genome is perceived as a complex tool for storage and dissemination of information. In a sense this isthe high-tech of bio-tech. And we are the hackers…learning how to crack the codes.”

Synthetic biology is a new branch of life science, which takes a constructive/building approach. It attempts to use biological components to construct new biological systems that do not exist in nature. “If we succeed in writing a sequence that predicts our output based on computerized rules that we found in the ‘Rosetta Stone’ – we can then use this ‘key’ to decipher certain sequences that appear inthe genome,” says Amit.

A new arrival at Technion, Amit is also recruiting a multidisciplinary team of students to take part in the international competition iGEM. “The walls between faculties are down,” he says, “…and our methods of teaching have to change accordingly.”

“In order to decipher and decode the genome, we need to make a biological Rosetta Stone. This is where Synthetic Biology comes into play.”

Did you know

The original Rosetta Stone is a granodiorite stele that had the sameancient text inscribed on it in three different languages, as a resultof which archaeologists were able to decipher Egyptian hieroglyphics.

Dr. Roee Amit

“We would like to understand what actually makes life special. Where the laws of physics and chemistry end and the laws of life begin...”

(l-r) Prof. Noam Ziv, Prof. Erez Braun, Prof. Ron Meir, Prof. Naama Brenner, Prof. Shimon Marom

At the Laboratory for Network Biology Research, researchers from four Technion faculties pursue an experimental and theoretical framework for the study of biological networks, pooling know-how to seek out the general mechanisms that allow for robust yet adaptive functionality.

“Thanks to the donation of Lorry Lokey we were able to renovate this part of the electrical engineering complex which facilitates our collaboration,” says Prof. Naama Brenner of the Faculty of Chemical Engineering. “Creative space, and the freedom to do research is basic to progress,” says Prof. Ron Meir, who approaches the

study of complex systems from the perspective of electrical engineering.

Like an inner sanctum of science, this is a place where developments in basic research take place today which will impact our world in a multitude of ways tomorrow. Brenner recalls lecturing alongside Technion Nobel Laureate Avram Hershko. “Some 30 years ago, no one thought much of the Nobel Prize-winning subject of ubiquitin. They were working just out of pure scientific curiosity,” she says. “It’s important to keep in mind that the applications of today rest on the foundations of several decades of basic science.”

vital networks

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proud 2B NobelThe three Technion Nobel Laureates pose for a photo at Technion’s cornerstone centennial celebrations

(l-r) Prof. Dan Shechtman, 2011 Nobel Laureate in Chemistry; Avram Hershko, 2004 Nobel Laureate in Chemistry, Aaron Ciechanover, 2004 Nobel Laureate in Chemistry and former Director of the Lokey Center.

In 2004, Israel won its first Nobel Prizes in Science. Prof. Avram Hershko and Prof. Aaron Ciechanover were awarded the Nobel Prize in Chemistry for their discovery of the ubiquitin system within living cells. Prof. Ciechanover had first hand experience of the multidisciplinary state of the art. A scientist at the Faculty of Medicine, the Nobel Prize in Chemistry coupled with the many applications that have emerged

out of the ubiquitin discovery convinced him of a real need to invest in the cultivation of the Nobel Laureates of tomorrow. By providing top facilities, through streamlining and boosting cross-faculty cooperation, and by harnessing Technion’s innate strengths – in engineering, basic science and applied innovation – the Technion in Israel could be set to take great steps on behalf of humanity and the world life science.

Since then, the Nobel Prize was awarded once again to a faculty member, and Prof. Dan Shechtman, who, like Hershko and Ciechanover, shares the vision of the power of synergy between pure science and direct application. Today, the Lokey Center has come to life – at the forefront of synergy where all sciences converge to unveil the secrets of life – putting them to work for the benefit of Israel and all humanity.

Calling future Nobel Laureates...

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In its brief course lie all the verities…”

such is Life

The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering was established in 2006 thanks to the generosity and vision of Lorry Lokey. Lokey has been widely recognized for his achievements in the field of journalism, as well for his civic and philanthropic endeavors. He has a distinguished record of community service focusing on educational institutions. He has shown vision by contributing to the development of truly innovative research in science with major gifts to wide range of programs. In keeping with his belief that science education and excellence are crucial, he also supports the Leo Baeck high school with the aim of motivating its students toward academic study and research.

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NetworkBiology

Life Sciences and Engineering Infrastructure

Proteomics Tissue Regeneration

Biomedical Optics

Developmental Gene Networks

Education

Bioinformatics

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“Look to this day for it is life.

The very life of life.

In its brief course lie all the verities

and realities of your existence:

The bliss of growth,

The glory of action,

The splendor of beauty.

For yesterday is but a dream,

and tomorrow is only a vision.

But today well lived makes every

yesterday a dream of happiness

and every tomorrow a vision of hope.

Look well, therefore, to this day.”

- Kalidasa, Sanskrit Poet

Out of darkness, mystery is born. Through freedom of thought,

mystery becomes understanding. This opens the promise of transformation.

The Lokey Center at Technion - where light is put on the science of life.

the secrets of life

Documents

revolution of life sciences

convergence revolution

confluence of life sciences

lokey interdisciplinary

genomic revolution

physical sciences

engineering lse

molecular biology revolution