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Assistant Professor Daphne Weihs from the Technion Faculty of Biomedical Engineering has developed a method for estimating the metastatic potential of tumors. Since 90% of cancer deaths are due to metastases,  their early prediction can improve the patient’s chances of survival

A research approach developed at the Technion will allow early and rapid prediction of metastasis formation. This information will enable physicians to treat these metastases in their early stages of formation, thereby improving the patient’s chances of survival.

The aforementioned approach, which was first presented in 2013 and whose development has continued in several directions since then, is presented in three papers published recently by Assistant Professor Daphne Weihs from the Technion Faculty of Biomedical Engineering. Professor Weihs, head of the Mechanobiology of Cancer and Wounds Lab, is studying the mechanical forces exerted on the body tissues by metastatic cells – cells with high metastatic potential that are highly invasiveness. The study was conducted using synthetic gel surfaces produced in Professor Weihs’s lab, which simulate the rigidity of soft tissues in the body. The goal: to quantify the metastatic potential and metastatic risk of cancer cells using the mechanical interactions of the cells with the gel to rapidly. Lab experiments test the forces that such cells exert on these synthetic surfaces to indent and penetrate them.  

Contrary to the treatment of primary tumors, which is now performed very efficiently, the treatment of metastases is complex and challenging. These metastases are sent to healthy organs via the lymphatic system and blood vessels, and it is difficult to identify them in their initial stages of development. When they are identified, usually at the point where they are already large and diffuse, medical treatment is very complicated. This is why metastases are responsible for 90% of cancer deaths.

In recent decades, various methods for identifying the metastatic potential of cells have been developed, based primarily on genetic and biological markers. The disadvantage of these measures is that they are expensive, take a long time and are not applicable to cancers such as pancreatic cancer, for which identifying markers have not yet been determined. In fact, up to now, no method has been presented that is effective, precise and general enough for quantifying the metastatic potential, an essential step towards predicting the formation of metastases.

In her research, Professor Weihs found that changes in the cell’s structure and its ability to exert a mechanical force may provide this essential information in a precise and quantitative way. This method, which is independent of the specific genetics of the tumor, enables measurement that is rapid (within a hew hours) and customized to the patient.

The synthetic gel surfaces produced at Professor Weihs’s lab  have stiffness that is similar to soft tissuesstiffness, and therefore they can be used to study the conditions under which cells exert force on the tissue that they attempt to penetrate. This method makes it possible to quantify the degree of force that they exert, the resulting penetration depths, and the difference in the behavior of different types of cells. “The cancer cell strives to penetrate normal tissue and take over the space inside it,” explains Assistant Professor Weihs, “so the cancer cells adapt and develop structural flexibility that enables them to soften or stiffen in order to squeeze or push through narrow areas.”

Based on the characteristics and structure of the healthy tissue, the cancer cells alter their own features, changing shape, internal structure and structural rigidity. “It is interesting to note that under certain conditions the secret of cancer cells is not hardness but rather softness – cancer cells are softer and more flexible than healthy cells, and metastatic cells are even softer and more flexible. In many cases, however, the cells need to apply force to push their way through. Cancer cells adapt to changing environments quickly, and our method is based on identifying changes in them.”

Three Papers

The first of the three papers was published in the journal Biomechanics and Modeling in Mechanobiology and is based on the research thesis of master’s student Sonbula Massalha. This study focused on cells that anchor themselves to their environment, but do not try to penetrate the synthetic gels produced in the lab. Massalha and Weihs observed a difference between benign and cancerous breast cells, where the latter exert greater force on the gel even though they do not try to penetrate it. These cells, although they are not yet invasive at that stage, affect the surrounding cells and can improve their ability to penetrate and invade. The phenomenon of synergy between neighboring cells is demonstrated in another paper.

The second paper was published in the journal Tissue Engineering, together with postdoc Dr. Martha Alvarez-Elizondo. This study focuses on the connection between the cell’s migratory capability and their mechanical invasiveness, which is measured in the laboratory on the gels. Principal findings: strong and aggressive is also the fastest moving. Cells belonging to sub-populations that are more capable of rapid migration are also the ones that exert more force in an attempt to penetrate the tissue or the gel. In this study Professor Weihs’s lab found that the mechanical testing method that they had developed is far more efficient and economical than conventional methods for testing these characteristics, and provides an assessment of the cells’ characteristics within a few hours.

For the third paper, published in the journal Annals of Biomedical Engineering, Prof. Weihs and doctoral student Yulia Merkher evaluated group invasion processes, which are more similar to those occurring in the body. In this study, the researchers found that cells become stronger and more invasive when they are in spatial proximity to each other, and the explanation is simple: cells that work together exert enhanced joint pressure on the tissue or aid each other in force application, thereby increasing their chances of penetrating tissue. Professor Weihs said: “With this discovery, we intend to go further and develop a tool for rapid and quantitative prediction of metastasis based on this group forcefulness allowing increased invasiveness, measurabkle using the gels, and on movement of cells in a group.”

Cancer cells, it turns out, create a different interaction with the tissue. Not only is the vertical force that they exert on it stronger, but even the adherence preceding the penetration attempts is carried out with greater force and with increased cell motility. “The cancer cell remains round, with a small area of contact, while benign cells become elongated and increase the area of contact with the tissue. It can be said that benign cells are busy solely with adherence and normal function, while a cell with metastatic potential is focused on changes in itself and its environment that will allow it to penetrate the tissue. To do so, the metastatic cell organizes itself very differently in terms of structure, and communicates in a mechanically different way with the other cells in its vicinity and with its environment. These are the clues that may help us identify such cells earlier and faster, on the basis of their mechanical characteristics. These abilities are obviously caused by genetic changes, but with the approach that we have developed, there is no need for information about the specific genetic changes.”

Currently, based on approval by the Ethics Committee that was obtained in 2015, Professor Weihs is evaluating the approach developed at her lab on tumors (not metastases) removed from patients with breast cancer, pancreatic cancer and gastric cancer, as well as tumors from patients with Ewing’s sarcoma, which is characteristic of children and adolescents. Professor Weihs explains that the study utilizes the “remains” of tumor tissues that are not needed, not even for pathology examination. “Based on the initial findings, it seems that we really are able to identify the sub-populations of metastatic cells in different cancers according to their mechanical features. Our practical goal is to develop a system which, during a biopsy or surgery, will enable the medical team to evaluate the likelihood of the presence of tumor metastases in other organs, and to estimate which organs are involved. As stated, this is a very quick test, such that within two or three hours the doctors will be able to assess the metastatic risk of the tumor and adjust the continued treatment accordingly.”

Assistant Professor Daphne Weihs earned her three degrees at the Technion Faculty of Chemical Engineering. She then did her postdoc at the Department of Pathology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). In her postdoc, which was financed by NASA because of its implications for biology and medicine in space conditions, she began to study her current subject: cell mechanics, with an emphasis on cancer cell behavior. She was on the list of Israel’s 50 most influential women in 2015, published by the newspaper Lady Globes, thanks to her discoveries in the diagnosis of tumor metastasis, which represent a “breakthrough that will save lives in the future.” 

Paper 1: https://link.springer.com/article/10.1007%2Fs10237-016-0864-4 

Paper 2: http://online.liebertpub.com/doi/abs/10.1089/ten.TEC.2016.0424

Paper 3: https://link.springer.com/article/10.1007/s10439-017-1814-8?wt_mc=Internal.Event.1.SEM.ArticleAuthorOnlineFirst

 

Nature Communications reports a paradigm shift in functionalizing molecules by Technion researchers

Researchers at the Technion’s Schulich Faculty of Chemistry have reported a paradigm shift by functionalizing organic molecules at a very distant position of the most reactive site. The article, published in the journal Nature Communications, is co-authored by Prof. Ilan Marek, head of The Mallat Family Laboratory of Organic Chemistry, Dr. Sukhdev Singh (a postdoctoral student from India), Jeffrey Bruffaerts (a doctoral student from Belgium) and Dr. Alexandre Vasseur (a postdoctoral student from France).

The practice of constructing molecules of carbon is called organic synthesis and it is at once an exact science and a fine art. Synthetic chemists have perfected this science to the point where not only can genes and proteins can be synthesized, but also an array of complex and fascinating molecular structures can be assembled on demand and tested for various applications. Such useful compounds range from biological tools and medicines to high-value materials, computers, sophisticated machines, and useful devices.

Organic synthesis derives its power from chemical reactions, reagents, and conditions, and synthetic strategies – a field in which several leading researchers have already won the Nobel Prizes. “You could see us are molecular architects,” explains Prof. Marek, “and as any architects that have to plan constructions, we as synthetic organic chemists, are planning the construction of important molecular framework following well-established rules”. However, continues Prof. Marek “in my research group, we are building molecules in a non-classical way and our approaches are always meant to solve the most acute synthetic problems in our field coupled with efficiency and elegance.” Classically organic chemists functionalize molecules at the most reactive sites but in the present study, the research group of Prof. Marek was interested to functionalize molecules at the less reactive position by using a transfer of chemical information along the molecular backbone of the molecule. This concept of “remote functionalization” could formally open the door to synthetic transformations that were not available before to the synthetic community.

“The idea of remote functionalization was proposed several decades ago,” explains Professor Marek, “but the field was in its complete infancy due to the major synthetic problems that it generated”. Now, as stated, the group has managed to transfer chemical information from the original location of the functional group to a very remote point in the molecule, in a single process (one-pot operation) and independently of the molecular distance between the two points. Moreover, by using a strained structure in the molecular backbone, the migration of the information releases the strain and allows the creation of several chiral carbon centers (a carbon atom with four different substituents can exist in two distinct stereochemical orientations, which are related to one another as any object is to its mirror image, is called chiral carbon center), that might have far-reaching applications in the academic world, but also for chemical industries and in particular for pharmaceutical companies.  

Prof. Ilan Marek was born in Israel and moved with his family to France at the age of 18 months. In 1988 he completed his doctorate at the University Pierre and Marie Curie in Paris, and after a short postdoctoral stay in Belgium, he returned to the same university as an independent researcher. In 1997, after 34 years in France, he returned to Israel and joined the Schulich Faculty of Chemistry at the Technion-Israel Institute of Technology. He now heads the Mallat Family Laboratory of Organic Chemistry and holds the Sir Michael and Lady Sobell Academic Chair. Prof. Marek has won numerous awards, including the Weizmann Prize for Exact Sciences, the Israel Chemical Society Award for Excellence, the Janssen Pharmaceutica Prize for Academic Excellence, the Royal Society Chemistry organometallic Award, the Yigal Alon Fellowship, the Michael Bruno Memorial Award, the Taub Award for Academic Excellence, the ERC advanced research grant and awards for excellence in teaching, including the Yanai Prize awarded by the Technion. He is also member of the scientific advisory boards of many journals in organic chemistry.

Link to the article

Around 700 excelling female high-school students from all over the country visited Technion as part of the Tech Women 2017 conference, organized to encourage young women to opt for academic studies in science and engineering.

From Kiryat Shmona all the way to Ma’ale Edomim; from Kibbutz Sasa to Ashdod: around 700 excelling female high-school students visited the Technion last Thursday, in honor of the annual Tech Women 2017 conference held by the Technion on International Women’s Day on March 8th. “Studying at the Technion means making the world a better place through science and engineering,” said Prof. Orit Hazan, Dean of Undergraduate Studies, in her opening remarks.

The conference, which took place courtesy of The Rosalyn August Foundation for the Empowerment of Young Women, was designed to encourage excelling female high-school students to choose science and engineering for their academic studies.

The participants were students majoring in 5-pt. mathematics and the fields of science and technology. They met with female researchers and staff members, Technion graduates and current graduate students. They toured labs and were exposed to the various research and study subjects in the different faculties.

“You are here because you were chosen, because we are positive that your future lies here, at the Technion,” said Orly Reiss, an alumnus of the Technion’s Faculty of Aerospace Engineering, who moderated the opening ceremony. After the opening event, each student visited two of the nine hosting faculties: Electrical Engineering; Computer Science; Mechanical Engineering; Aerospace Engineering; Civil & Environmental Engineering; Chemical Engineering; Materials Science & Engineering; Chemistry; and Physics.

“In the very first graduating class of the Technion, which opened in 1924, there were 16 men and one woman,” said Prof. Peretz Lavie, President of the Technion. “Today about 37% of our undergraduates are women, and our goal is to reach 50% in all the departments. This special day is dedicated to persuading female high-school students that they belong here at the Technion and that they are able to do so. The future of the State of Israel depends on scientific and engineering knowledge, and we look forward to seeing these students here in a few years attending the Technion’s opening ceremony at the beginning of the academic year.”

Dr. Tzipi Horowitz-Kraus of the Faculty of Education in Science and Technology, said: “It is very exciting to see the future generation of female scientists of Israel.” She urged the students to approach their studies passionately and consciously. She spoke of her own brother, who was extremely intelligent but had difficulties reading, and of her decision to specialize in the field of language acquisition. Dr. Horowitz-Kraus, who is the founder of the Technion’s Educational Neuroimaging Center, shared her discoveries regarding the connection between brain development and the development of language and reading skills in infants and children. “I examine the child’s brain as he or she listens to a story, and try to understand the processes taking place and the way listening improves future reading skills.”

Sarah Nagosa, a PhD student at the Ruth & Bruce Rappaport Faculty of Medicine, discussed the topic of her dissertation: eye diseases and their treatment. Nagosa immigrated to Israel from Ethiopia at the age of three, and grew up in Kiryat Malachi.    “I only first heard of the Technion when I was 17 years old, when several American donors came to visit my high school. I decided that day that this is what I want to do – to attend the Technion. Of course, I had apprehensions – what if I’m not accepted? What if I’m not smart enough? But I applied for admission and was accepted to the Faculty of Biology. The beginning wasn’t easy – I felt so small and the campus was so huge. It was hard for me to find common ground with the rest of the students. But I slowly realized that we all had the same apprehensions, and I suddenly found the courage to ask questions. Today, working on my research and serving as a teaching assistant at the same time, I can tell you that while the Technion might be tough academically, it is “soft” and simple in every other way: the dorms, tutoring and any other form of assistance. The difficulties have not disappeared, but I’ve learned to overcome them, knowing that my ultimate goal is worth it.”

Aldana Grichener, who is now publishing her first scientific article, began studying at the Technion in the Rothschild Scholars Technion Excellence Program around 18 months ago.

Grichener, 21, was born in Argentina and immigrated to Israel with her family as a baby. She was accepted into the MOFET (mathematics, physics and community culture) program at Makif Zayin comprehensive high school in Ashdod, and at the early age of 15 she decided to attend the Technion, “because scientific research attracted me and I knew that the Technion is the best place for it.” Three days after her discharge from the IDF she began her studies at the Technion, and in her first semester she attended a course taught by Prof. Noam Soker from the Faculty of Physics. “I liked his attitude as a lecturer and as a person – he does everything for his students and is always willing to talk to them outside office hours. I read his articles and thought it would be interesting to work with him, so I approached him and asked him to be my undergraduate project advisor.” Prof. Soker assented to her request, which has led to an article that will soon be published in the journal Monthly Notices of the Royal Astronomical Society. The topic: a new model for the formation of the “Mickey Mouse ears” that characterize many supernova remnants.

Supernova is a phenomenon typical of heavy stars at the end of their lives. This process begins with the collapse of the star into itself, an event in which the radius of the inner part known as the core shrinks, becoming a thousand times smaller. In this process, in which the inside of the star shrinks to a diameter of about 20 km, a neutron star of enormous density is created: one billion tons per cubic centimeter. The shrinking, which is the result of gravitational force, is stopped at some point and replaced by a huge explosion that expels the star’s outer shell – the parts that remained during the shrinking process – at a speed of millions of km per hour.

“When we study the morphology of supernova remnants, we find that a third of them have two ‘ears’ protruding from the main body. The usual explanation for supernova explosions fails to explain the ear phenomenon, and in this paper we propose an alternative model consistent with various simulations, observations and calculations.”

According to Grichener’s and Prof. Soker’s model, the ears are formed by the emission of jets launched during the explosion of a star or shortly afterward. These gas jets are emitted as a result of the rapid rotation of the core that precedes the collapse, and they carry an enormous quantity of kinetic energy. “On the way, these jets encounter exploding gas, and this encounter inflates the ears that we see. Therefore, we claim that a paradigm shift should be made in the explanation of the explosion of heavy stars, known as the core-collapse supernova.

Sharon Yavo Ayalon, a doctoral student at the Technion Faculty of Architecture and Town Planning, has won first place in the President’s Scholarship

“The journey of a researcher is very personal and lonely.  Most of the time we do and write things that we know that no one will read, and this moment of winning the President’s Scholarship is an extremely rare moment of applause, not only in the physical sense of the word but mainly in the knowledge that we have partners: that a very respectable group has read, understood and realized that what we do is important and relevant and valuable.”

These statements were made by Sharon  Yavo  Ayalon, a doctoral student at the Technion Faculty of Architecture and Town Planning, at the President’s Scholarship award ceremony on February 13. This year, nine doctoral candidates – eight women and one man – received the President’s Scholarship awards. The title was the New Israeli Order: the Boundaries of Fraternity and Equality.

Yavo Ayalon, who received first prize in the sum of NIS 150,000, was born and raised on Kibbutz Hulata in the Hula Valley. She came to Haifa to attend the Technion and her three children were born here. Today, after completing her BSc and MSc at the Technion Faculty of Architecture and Town Planning, she is working on her doctorate at the Faculty. In addition to her studies, she teaches Basic Design at the Faculty.

She began her undergraduate studies in 1996, after which she spent six years working at an architecture firm, “but my longing for academia brought me back to graduate school, during which I served as curator of the PeKA Gallery (Paul Konrad Hoenich Center for Art, Science and Technology) at the Faculty.” The subject of her MSc, under the guidance of Professor Nurit Lissovsky and Professor Michael Levin, was land art in Israel: a discussion of three local artists who strive in their work for the construction and understanding of the local Israeli identity and create art as a way to connect with the place.

In March 2015, loyal to the Technion Faculty of Architecture and Town Planning, Yavo Ayalon began her doctoral studies in town planning, under the guidance of Associate Professor Tal Alon-Mozes and Dr. Meirav Aharon Guttman. Topic: Presentation of Urbanism – the Relationship between Art, Space and the Public. “I came to architecture from art – first painting and sculpting and then performance art – and my academic work has always stemmed from the desire to link these worlds.”

Her case study in her doctoral thesis is the city of Acre. “My question is whether and how theater art, which plays a central role in Acre’s cultural activity, affects the intra-urban borders. Cities today are highly segregated and fragmented – each city is a mosaic of communities, and this is clearly evident, of course, in Acre, where there are diverse populations: Jews, Arabs, immigrants from the former Soviet Union, and others. In the main, I examine the soft borders, i.e. borders that are not made of fences and walls, but rather by people’s decisions – each community chooses the geographic area where it will not only live but also consume culture, raise its children and so on. My method combines spatial architectural research with social research. Therefore, in Acre, beyond archival research and architectural analyses of space, I carry out ethnographic field work. And since the relevant art is theater, as part of my participant observation I am studying drama.”

She submitted the President’s Pcholarship forms at the last minute and without high expectations, but it was clear to her that her research work on boundaries was very relevant to the theme of the scholarships this year – the boundaries of fraternity and equality. “I would like to tell doctoral students of both sexes that it’s worth their while to apply for grants and scholarships, because there are always pleasant surprises. For me this is a significant scholarship, which will help me devote my time to my doctoral research.”

The Israel President’s Scholarships for Scientific Excellence and Innovation are intended to “encourage quality academic research, foster groundbreaking scientific endeavors and promote scientific excellence and innovation in Israel.” The scholarships are funded through a special allocation of monies from the Estates Committee at the Ministry of Justice.

 

Lady-Tech Conference at the Technion: Learning from the experience of female Technion graduates who hold key positions in industry and academia

“It is important to choose a direction and follow it with all your might. Believe in yourselves and your gut feelings, take the lead, ignore pangs of conscience, don’t be ashamed and don’t apologize. Career advancement is not always meteoric, so it’s important to stop every now and then; but in the end dreams do come true, so don’t stop dreaming”.

These are just a few of the tips given by Technion female graduates to their counterparts, students and graduates alike, at a panel held on the topic of “The Greatest Challenges on the Way to the Top”, which took place at the Technion as part of the 3^rd Lady-Tech Conference. The panel, which was moderated by Professor Ayelet Fishman from the Department of Biotechnology and Food Engineering, consisted of Dr. Avital Schrift – Director of MABAT Missiles at Israel Aerospace Industries Ltd.; Colonel (Reserves) Adi Bershadsky who is engaged in high-tech international marketing; Iris Han – CEO of the Nature Protection Society; Prof. Hagit Attiya – Technion VP for Academic Affairs; Hanna Sarel – CEO of Medatech Information Technologies Ltd.; Karin Aibschitz Segal – Hardware and Software Operations Manager at Intel Israel; and Marie Attala Libbs – owner and CEO of Nazareth Electricity Engineering.

The conference was the initiative of the Technion Alumni Association and the ‘Supersonas’ organization, and the participants were all female. The opening remarks were given by Technion Alumni Association Chairperson Sigal Fierst, CEO and owner of CTS Israel: “I believe that 30 years from now no one will mention the percentage of Technion female graduates, and gender-focused events will no longer be held,” said Fierst, “because the significant contribution of female graduates will be something that is taken for granted.”

“Sticky-floor” Syndrome

Technion graduate Yulia Kagan, Business Development Manager at Leidos Israel, spoke about women at the beginning of their careers. “Many women do not step on the career acceleration-pedal once they decide to start a family, and long before they have their first child. Before we address breaking the glass ceiling we need to address the ‘sticky floor’, which stems primarily from the way women see the progression of their lives and their future careers”.

Tali Heruti Sober, Editor of the labor market section in “The Marker” newspaper, lectured on “Men, women and the economics separating them”. According to her, wage discrepancies of 33% still exist between men and women, and in high-tech they approach 45%. “There are several reasons for this. Firstly, women don’t like to take risks. Secondly, the enemy of the working woman is her time-clock attendance card. Thirdly, women are more loyal to their work place than men, and it’s well known that wages are not upgraded significantly without changing your work place. A similar process is happening in entrepreneurship – a woman who builds a venture treats it like her baby, nurturing and raising it over the years, while men prefer serial entrepreneurship and tend to jump from venture to venture”.

Engineers and scientists at the Technion are increasing collaborations to intensify and expand research and development in neuroscience and technology.

In recent years, researchers from diverse Technion faculties have forged an open connection in order to expand and deepen the study of brain function, from high-order cognition to basic biological mechanisms: decision making; learning and memory; sensory perception; motor control; the relationship between the immune system and the brain; basic biological processes in neurons and supportive cells in the brain; communication between neurons and more. Beyond understanding how the brain works, several researchers are also looking for ways to repair damage to the brain and to find solutions to neurological diseases.

For example, Prof. Miriam Zacksenhouse of the Faculty of Mechanical Engineering is developing technologies for operating electronic devices using brain activity. Prof. Yoram Gutfreund of the Rappaport Faculty of Medicine is studying the owl’s unique auditory system and spatial orientation. Prof. Yitzhak Schiller of the Faculty of Medicine is inventing innovative methods for treating epilepsy and Parkinson’s disease. Prof. Ron Meir of the Faculty of Electrical Engineering is studying and developing artificial neural networks that are displaying unprecedented performance in the areas of learning and pattern recognition.

Prof. Ido Erev of the Faculty of Industrial Engineering & Management is a psychologist who studies basic decision-making and learning processes. “Today, after many years of behavioral research, I understand that physiological data from brain research will enable me to check whether my assumptions are correct and to gain a better understanding of  mechanisms such as decision-making,” he said.

Prof. Itamar Kahn of the Faculty of Medicine is using fMRI technology to study brain activity responsible for the integration of information from the sensory and motor systems. He also studies how failures in these processes can be responsible for developmental brain disorders. “Mainly, I’m trying to understand disruptions in this system, and it is clear to me that cooperation with engineers could lead not only to a better understanding, but also to interesting robotic applications that will be run directly on the brain and will aid in activities such as walking.”

Electrical Engineer Dr. Shahar Kvatinsky is developing non-standard computer architectures inspired by the brain, concentrating primarily on neuromorphic computers that mimic the operating mechanism of the cerebral cortex. “The classic computer comprises a calculation unit (CPU) and a storage unit (memory); which is not how the brain is structured, mainly lacking the brain’s ability to constantly change its connectivity. If we design computers that are inspired by the brain and contain components that function similarly to synapses and neurons, they will perform human activities such as face recognition far more efficiently than existing computers. Hence, the need for collaboration between engineers and neuroscientists,” he says.

“In recent decades, the field of brain research has become diverse and multidisciplinary,” explains Prof. Jackie Schiller of the Rappaport Faculty of Medicine. “Engineering tools are an integral part of the development of brain research and the application of brain devices as a solution for motor and cognitive impairments. Artificial systems that mimic the human brain have tremendous potential. Today, it’s clear to us that only synergy between the various biological, computational and engineering disciplines will lead to significant progress in our understanding of the brain and its functions. What we need here is extensive and multidisciplinary research activity based on coherent in-depth theoretical work and on preclinical and clinical studies.”

The new Technion-wide research group, headed by Prof. Jackie Schiller, includes researchers from many and varied faculties: Prof. Yonina Eldar (Electrical Engineering), Prof. Simone Englender (Medicine), Assistant Prof. Rakefet Ackerman (Industrial Engineering & Management), Prof. Naama Brenner ( Chemical Engineering), Assistant Prof. Omri Barak (Medicine), Prof. Yoram Gutfreund (Medicine), Assistant Prof. Dori Derdikman (Medicine), Prof. Hermann Wolosker (Medicine), Prof. Noam Ziv (Medicine), Prof. Alon Wolf (Mechanical Engineering), Prof. Miriam Zacksenhouse (Mechanical Engineering), Assistant Prof. Ronen Talmon (Electrical Engineering), Prof. Emeritus Moussa Youdim (Medicine), Prof. Eldad Yechiam (Industrial Engineering & Management), Prof. Ron Meir (Electrical Engineering), Prof. Shimon Marom (Medicine), Prof. Hillel Pratt (Medicine), Prof. Ido Erev (Industrial Engineering & Management), Assistant Prof. Itamar Kahn (Medicine), Assistant Prof. Shahar Kvatinsky (Electrical Engineering), Assistant Prof. Asya Rolls (Medicine), Prof. Yitzhak Schiller (Medicine) and other researchers.

Dendrites – the Brain’s Trees of Knowledge

An article by Prof. Jackie Schiller and doctoral student Maya Sandler sheds light on some basic questions related to the influence of the cerebral cortex on functional aspects such as emotions, thinking and psychiatric disorders. The article, published in the prestigious journal Neuron, examines brain plasticity mechanisms related to anticipation, feedback, learning and memory. The researchers anticipate that the findings may lead to the development of new approaches for treating learning and memory disorders and behavioral disorders such as autism.

The brain is composed of a complex network of interconnected neurons. The neuron, which is the basic processing unit of this network, is a complex processing unit that receives large number of input information from other neurons and processes them into an output that is transmitted to thousands of other neurons in the network.

The neuron is composed of several organelles: (1) the cell body and nucleus, which is responsible for the production of proteins and maintenance of the entire cell; (2) the axon, a branched offshoot that extends from the cell body and transmits information (output) to thousands of other neurons in the network; (3) the dendrites, the main input sites of the neuron, which enable the cell to receive and process information from the axons of thousands of neighboring cells; and (4) the synapses, the point of connection between the axon of one cell and the dendrite of another cell. All these channels of communication – axons, dendrites and synapses – are essential for brain function because they determine our motor, cognitive and other abilities.

Dendrites, which comprise most of the grey matter and occupy most of the volume of the cerebral cortex, have been the focus of Prof. Schiller’s research in recent years. They are tree-like branches, a few millimeters in length, which enable the cell to receive and process information from other neurons. In previous articles, Prof. Schiller demonstrated that dendrites are not simple structures but complex nonlinear processing  machines, and in this paper she presents a mechanism explaining a specific aspect of their unique flexibility. “During the learning process, this mechanism changes the dendrite and synapse. If we understand the precise nature of this mechanism we may be able to improve processes such as memory formation and potentially develop a novel class of treatment for neurodevelopmental and neurodegenerative diseases. Now we are focusing on understanding dendritic activity at the micro level but also at the network level in-vivo, with the hope of understanding the implications of these physiological mechanisms in health and disease.”

The Technion presents: Science at the Bar, to mark International Women’s Day

Tuesday, March 7, 2017, starting at 20:00, at bars throughout the city of Haifa

In honor of International Women’s Day, which will be celebrated next week, seven Haifa bars will host leading female researchers from the Technion. “International Women’s Day is an excellent opportunity to present some of the groundbreaking research conducted by female researchers at the Technion,” said Professor Ayellet Tal, Advisor to the President of the Technion for the Advancement of Women in Science and Engineering. “The researchers will present surprising answers to questions at the forefront of current research in electrical engineering, medicine, biology, chemistry, biotechnology and architecture.” At the event, each of the seven researchers will lecture at one of Haifa’s bars, as follows:

The event is held under the auspices of Professor Ayellet Tal, Advisor to the President of the Technion for the Advancement of Women in Science and Engineering.

Space is limited – advance reservations required.

Reporters and photographers are welcome.

For further details: Doron Shaham – 050-3109088

Three-dimensional characterization developed by a Technion researcher and her colleagues in Illinois will promote miniaturization in semiconductor manufacturing

New technology developed at the Technion and in Illinois is expected to bring about a dramatic leap in the miniaturization of electronic devices. The study, which included researchers from the University of Chicago and from Argonne National Laboratory in Illinois, was led by Dr. Tamar Segal-Peretz, currently a faculty member at the Technion’s Wolfson Department of Chemical Engineering, during her postdoc at Chicago.

The study, published in the journal ACS Nano, focuses on the self-assembly of block copolymers – polymer chains that serve as templates in production processes (nano-fabrication). The paper presents the production of nano-templates using the self-assembly process of block copolymers and a new approach for characterizing the nano-templates. Using the block copolymers enables production in dimensions smaller than 10 nm, which is considered a complex challenge in the semiconductor industry.

Deep into the Layers

Miniaturization to small dimensions and the use of block copolymers requires a thorough understanding of the processes occurring deep in the layers. Dr. Segal-Peretz said, “Most of the tools currently available only examine the surface of the material, thus missing important information that is below the surface. The study now published shows that our approach – three-dimensional mapping of structures using scanning transmission electron microscopy (STEM tomography) is essential for understanding the self-assembly processes and creating nano-patterns whose quality is much higher. Combining molecular simulations with the three-dimensional information enables us to understand the interactions between the copolymers and the patterns on the substrate and the source of the spatial fluctuations in the nanostructures. Thus we are paving the way for designing and manufacturing improved patterns and devices, not larger than 5 nm in size – much smaller than the current components manufactured using nanolithography.”

Today, electronic devices are manufactured using photolithography – where light is projected through a mask. With this method, miniaturization of the templates for production is limited by the wavelength. Short wavelengths are necessary for small devices, and generating such radiation is a hard task. Dr. Segal-Peretz said, “The advantage of block copolymers is that the size of the template is determined by the chemistry of the polymer and not by an external factor such as wavelength.”

Directed Self-Assembly

But self-assembly alone is not sufficient for manufacturing purposes, because the location of the templates that are formed in this way is not controlled. “In order to direct the polymers to the desired position we use an initial template that is easy to manufacture, and the template directs the polymers. This process is called directed self-assembly. Combining this approach with existing photolithography processes enables us to overcome the limitations involved in producing nano-templates, while maintaining low costs.”

As stated, one of the challenges in manufacturing electronic components is the existence of defects in the template. This is a scientific and technological problem since without full identification of the defects below the surface, it is difficult to understand the source of the defects and therefore it is difficult to develop improved manufacturing methods. “Ultimately the world is three-dimensional,” said Dr. Segal-Peretz, “and therefore no two-dimensional representation of the world is sufficient.”

Three degrees at the Technion

Dr. Tamar Segal-Peretz completed all of her degrees at the Technion – after an undergraduate degree in Biochemical Engineering at the Department of Chemical Engineering, she worked in the industry on the development of night vision systems, and then entered the direct doctorate track at the Russell Berrie Nanotechnology Institute (RBNI). She completed her doctorate on polymer-based solar cells at the Department of Materials Science & Engineering, under the supervision of Prof. Gitti Frey. After her postdoc at the University of Chicago and Argonne National Laboratory, she joined the Wolfson Department of Chemical Engineering.

To the paper

The 3D structure of block copolymer nano-patterns, obtained through TEM tomography. The width of each nano-pattern is 10 nanometers.

The 3D characterization enables direct observation of the spatial fluctuations of block copolymers. Minimal fluctuations are desired for semiconductor nanofabrication. The movie shows a series of cross section images obtained from the 3D characterization.

Novel Amyloid Structure Could Lead to New Types of Antibiotics

HAIFA, ISRAEL (February 24, 2017) – The highly pathogenic Staphylococcus aureus bacteria is one of the five most common causes of hospital-acquired infections. In the US alone, approximately 500,000 patients at hospitals contract a staph infection. It is the bacteria responsible for MRSA, for which there is no vaccine.

But all that could change, thanks to groundbreaking findings to be published today in Science by a Technion-Israel Institute of Technology team led by Assistant Professor Meytal Landau of the Faculty of Biology. The researchers discovered, for the first time, unique amyloid fibrils through which the pathogenic and highly drug resistant Staphylococcus aureus bacterium attacks the human cells and immune system. The research could advance the discovery of antibiotics with a novel mechanism of action that will attack key bacterial toxins.

The researchers discovered ‘ammunition’ that assists the infectious bacterium: a novel form of an amyloid fibril whose three-dimensional structure was determined at atomic resolution, revealing the first-of-its-kind structure of this toxic fibril. Amyloids, which are proteins notoriously known for their association with neuro-degenerative diseases such as Alzheimer’s and Parkinson’s, form a network of protein fibrils – somewhat similar to a spider web – characterized by an orderly and extremely stable structure. This stability enables the proteins to withstand extreme conditions in which ordinary proteins do not survive.

One of the best-known examples of this is “Mad Cow” disease, which broke out in England in 1986. According to Prof. Landau, “This disease surprised the scientific community because its cause was not a virus, nor a bacterium, but a protein called Prion, possessing an amyloid-like structure. It then became clear that a protein can be transmissible, and due to its stability, it infected human beings who consumed the contaminated beef – meaning, the protein did not break down in the stages of meat processing, cooking and digestion.”

The “Mad Cow” prion, like all amyloids discovered so far, belongs to a group possessing what is called a cross-ß structure. In the present study, an amyloid of a completely new structure was discovered, which was named cross-α.

“At some point we knew that we had found something unique, but only after several trips to cyclic particle accelerators (Synchrotrons) in Grenoble and Chicago were we successful in verifying its being a new type of amyloid,” said Prof. Landau. “Much more work was required before we could publish our findings, but from the very first moment, it was clear to us that what we had was a paradigm shift.”

She estimates that the new discovery will lead to the development of antibiotics with a new action mechanism. Such drugs will inhibit the amyloid formation thereby neutralizing one of the important ‘weapons’ in the arsenal of this pathogenic bacterium. In her opinion, since this antibiotic is not aimed at killing the bacterium but only reducing its toxicity to humans, it will not lead to a rapid development of bacterial resistance towards it.

“Resistance to antibiotics develops in bacteria due to evolutionary pressure – natural selection leads to the growth of bacteria which antibiotics are unable to kill,” she said. “If we reduce the pressure on the bacterium and don’t kill it but rather prevent its pathogenic aspects, the resistance will probably not rush to develop.”

When looking towards the future, Prof. Landau clarifies that “in academia itself, it’s difficult to carry out a full process of drug development due to the prohibitive cost entailed. Nevertheless, we can provide drug developers with scientific knowledge that will accelerate and lower the costs of the process. The present discovery is a stepping-stone in that respect. Now our challenge is to find the substance that will impede the cross-α fibril, thereby ‘disarming’ the bacterium.”

“From the scientific standpoint, there is an important lesson here – thinking out of the box opens new doors,” she continued. “In this specific case, extending the repertoire of amyloids. Deciphering new structures of amyloids might lead to new insights regarding mechanisms of neurodegenerative diseases. It might also lead to the discovery of ‘good’ amyloids that take part in an organism’s natural protection against infections. Such research could lead to the development of novel means of protection against the toxins found in bacteria and fungi.”

The research was conducted by members of the Landau lab, including Einav Tayeb-Fligelman, Orly Tabachnikov, Asher Moshe and Orit Goldshmidt-Tran, with the assistance of Michael Sawaya from the University of California Los Angeles (UCLA), and of Nicolas Coquelle and Jacques-Philippe Colletier from Université Grenoble, France.

After completing her B. Pharm degree at the Hebrew University in Jerusalem, Assist. Prof. Landau went on to pursue her two advanced degrees at Tel Aviv University – an MSc in Neurobiology and a PhD in Structural Bioinformatics. After attaining her PhD, she relocated for five years to do her post-doctorate with Prof. David Eisenberg at UCLA, where she specialized in x-ray microcrystallography and amyloids associate with Alzheimer’s disease.
After completion of her post-doctoral research, she said, “I chose the Technion thanks to, among other things, its superior research infrastructures. The Technion Center for Structural Biology (TCSB), founded at the initiative of Israeli Nobel Prize Laureate and Research Professor Aaron Ciechanover at an investment of $5 million, features state-of-the-art infrastructure which makes it possible to determine protein structures at atomic resolution.”

Through the years, Assist. Prof. Meytal Landau was awarded numerous scholarships and research grants, among them by the Israel Science Foundation, U.S.-Israel Binational Science Foundation, Alon Fellowship from the Israeli Council for Higher Education, I-CORE – Israeli Centers Of Research Excellence, the Marie Curie CIG by the European Commission, and the German-Israeli Project Cooperation (DIP).

Photo Exhibition of Campus Life

The photographs displayed in this exhibition portray past campus life juxtaposed with contemporary images. Historical prints were scanned from the Technion’s archive collections, and contemporary photos were selected from digital photo galleries.

The impetus for the exhibition came from a project for digital scanning of the Technion’s Nessayahu Historical Archive, located in the Elyachar Central Library and stored under controlled conditions. The archive includes thousands of items that document the history of the Technion, beginning in 1912 with construction of the original Technion building (then known as the “Technikum”) in Haifa’s Hadar neighborhood. The digitalization process has tremendous significance for documenting, preserving, and making this history accessible to future generations.

The exhibition organizers examined hundreds of photos, finally choosing those that focus on the human angle of campus life. Subsequently, contemporary photos were sought, in digital collections or on Internet sites, that document parallel situations.

These evocative photographs, portraying people and events at different points in time, speak for themselves. They inspire viewers to sail on the wings of knowledge and imagination, and compare past and present norms and fashions, body language, leisure activities, buildings, and changing landscapes.   

Curator: Anat Har-Gil.

Sperm-Egg Fusion Proteins Have Same Structure as Those Used by Zika and Other Viruses to Invade Healthy Cells

HAIFA, ISRAEL (February 14, 2017) – The protein that helps the sperm and egg fuse together in sexual reproduction can also fuse regular cells together. Recent findings by a team of biomedical researchers from the Technion-Israel Institute of Technology, Argentina, Uruguay and the U.S. show this protein is part of a larger family of proteins that helps other cells bind together to create larger organs, and which also allows viruses like Zika and Dengue to invade healthy cells.

For every sexually reproducing organism, sperm and egg fusion is the first step in the generation of a new individual. This process has been studied for more than 100 years in many organisms including humans, mice, insects, plants, sea urchins and even fungi. But the identity of the molecular machineries that mediate sperm and egg fusion remained unknown.

Now, the team led by Dr. Benjamin Podbilewicz, of the Technion Faculty of Biology, and Pablo S. Aguilar of Universidad Nacional de San Martin in Argentina, has demonstrated that the protein HAP2 – a long known player in sperm-egg fusion – is a protein that mediates a broad range of cell-cell fusion.

HAP2 is found in plants, protists (e.g. algae, protozoa, and slime molds) and invertebrates, and is therefore considered an ancestral protein present at the origins of the first eukaryotic cells (cells with real nuclei). However, a closer look at HAP2 led the researchers to conclude that HAP2’s roots are even older. Structural and phylogenetic analysis of HAP2 proteins revealed they are homologous to proteins used by viruses such as Zika and Dengue to fuse viral membrane to the membrane of the cell they invade.

According to the researchers, this means HAP2, FF and viral fusion proteins constitute a superfamily of membrane fusion proteins, which the authors named Fusexins (fusion proteins essential for sexual reproduction and exoplasmic merger of plasma membranes).

“Fusexins are fascinating machines that keep a structural core diversified to execute cell membrane fusion in very different contexts,” says Prof. Podbilewicz. “Understanding the different structure-function relationships of fusexins will enable scientists to rationally manipulate cell-cell fusion in fertilization and tissue development. The added and very timely benefit is that it provides us greater understanding of how Zika and other viruses cause diseases in their target hosts.”

Video: Cytoplasmic mixing between three cells expressing HAP2 and RFPcyto. Three cells in the middle (boxed) merge their cytoplasms around time 3:15. It was then confirmed that the syncytium contained three nuclei using multifocal sectioning by spinning disc confocal microscopy (Fig. S1). Another cell undergoes karyokinesis around time 3:45 (arrow). 

The striking similarities between proteins that promote membrane fusion under very different contexts led the authors to dig into mechanistic details. Performing cell-cell fusion experiments, the researchers demonstrated that, like FF fusexins, HAP2 is needed in both fusing cells to promote membrane cell fusion. This bilateral requirement of HAP2 and FF fusexins differs from the viral mechanism of action, where fusexin is only present in the viral membrane (see figure).

The combined conservation of structure, sequence, and function imply that these proteins diverged from a common ancestor. Fusexins might have emerged 2-3 billion years ago to promote a primordial form of genetic material exchange between cells. Later, enveloped viruses took these fusion proteins to infect cells more efficiently. Finally, multicellular organisms adapted fusexins to sculpt organs like muscle and bone-repairing osteoclasts in vertebrates and skin and the vagina in worms through cell-cell fusion.

To the Paper in The Journal of Cell Biology