Month: February 2017

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

How Hydras Know Where to Regrow Lost Body Parts

Few animals can match the humble hydra’s resilience. The small, tentacled freshwater animals can be literally shredded into pieces and regrow into healthy animals. A study published February 7 in Cell Reports suggests that pieces of hydras have structural memory that helps them shape their new body plan according to the pattern inherited by the animal’s “skeleton.” Previously, scientists thought that only chemical signals told a hydra where its heads and/or feet should form.

Regenerating hydras use a network of tough, stringy protein fibers, called the cytoskeleton, to align their cells. When pieces are cut or torn from hydras, the cytoskeletal pattern survives and becomes part of the new animal. The pattern generates a small but potent amount of mechanical force that shows cells where to line up. This mechanical force can serve as a form of “memory” that stores information about the layout of animal bodies. “You have to think of it as part of the process of defining the pattern and not just an outcome”, says senior author, biophysicist Kinneret Keren of the Technion – Israel Institute of Technology

When pieces of hydra begin the regeneration process, the scraps of hydra fold into little balls, and the cytoskeleton has to find a balance between maintaining its old shape and adapting to the new conditions. “If you take a strip or a square fragment and turn it into a sphere, the fibers have to change or stretch a lot to do that,” explains Keren.  However, some portions retain their pattern. As the little hydra tissue ball stretches into a tube and grows a tentacle-ringed mouth, the new body parts follow the template set by the cytoskeleton in fragments from the original hydra.  

The main cytoskeletal structure in adult hydra is an array of aligned fibers that span the entire organism. Tampering with the cytoskeleton is enough to disrupt the formation of new hydras, the researchers found. In many ways, the cytoskeleton is like a system of taut wires that helps the hydra keep its shape and function. In one experiment, the researchers cut the original hydra into rings which folded into balls that contained multiple domains of aligned fibers. Those ring-shaped pieces grew into two-headed hydras. However, anchoring the hydra rings to stiff wires resulted in healthy one-headed hydras, suggesting that mechanical feedbacks promote order in the developing animal.

Hydras are much simpler than most of their cousins in the animal kingdom, but the basic pattern of aligned cytoskeletal fibers is common in many organs, including human muscles, heart, and guts. Studying hydra regeneration may lead to a better understanding of how mechanics integrate with biochemical signals to shape tissues and organs in other species. “The actomyosin cytoskeleton are the main force generator across the animal kingdom,” says Keren. “This is very universal.”

To the Paper in Cell Reports

Technion alumnus Moshe Yanai highlighted the depth of service exemplified through recipients of the Yanai Prize for Excellence in Academic Education. The annual Technion ceremony added new prize categories, including an educational initiative grant; and commendation in teaching.

Six outstanding professors at the Technion Faculty of Biotechnology and Food Engineering received the Yanai Prize for Excellence in Academic Education this year. In addition to prizes for excellence, new categories were added for education in entrepreneurship and special commendation for teaching.

The ceremony was attended by Moshe and Rachel Yanai, the Technion Board, the winners and their families, lecturers and students. The prestigious prize was awarded for the sixth consecutive year: “In appreciation of faculty members, who set an example through their endless contributions to teaching and learning and for their efforts to improve student involvement and sense of belonging to the Technion.”

The six prize recipients this year are:  

• Assistant Professor Oded Amir (Faculty of Civil and Environmental Engineering),
• Professor Eli Boehm (Faculty of Computer Science),
• Dr. Ari Gero (Faculty of Education in Science & Technology),
• Prof. Ron Holtzman (Faculty of Mathematics),
• Assistant Professor Guy Bartal (Faculty of Electrical Engineering)
• Professor Sima Yaron (Faculty of Biotechnology and Food Engineering).

The Yanai educational initiative grant was awarded to the vertical-thematic studio (which was established at the Faculty of Architecture and Town Planning). Teaching commendations were awarded to Professor Dan Ritter (Faculty of Electrical Engineering), Associate Professor Yossi Gil (Faculty of Computer Science) and Associate Professor Yoed Tsur (Faculty of Chemical Engineering).

Technion alumnus Moshe Yanai, donated $12 million for the establishment of the prize. Attending the ceremony with his wife Rachel, he said: “The prizewinners are people who put the common good before their own personal good. Academic promotion is based on publishing articles and obtaining research grants, and not on the quality of teaching, and therefore researchers like you, who invest time and effort in teaching, do so out of genuine altruism. Our contribution to the establishment of the prize is a catalyst for excellence in teaching, but no less important is the seriousness with which the Technion approaches this mission. Everyone talks about the importance of teaching in academia, but the Technion doesn’t merely talk about it. It does a lot in this area.”

Technion President Prof. Peretz Lavie spoke about the revolution taking place in the world of teaching and about the Technion’s commitment to play a significant role. “The monopoly on the retention and distribution of knowledge has been taken out of the hands of its historical gatekeepers, and now the pocket of every ten-year-old contains more computer power than the Apollo spacecraft.” he said. “Therefore, teaching shouldn’t be based on facts and content, but rather on imparting skills such as validation of information, integration of information from different sources and intelligent use of information for problem-solving. We must make sure that the training, skills and knowledge that we impart to our students will be relevant not just a few years after graduation, but throughout their professional lives.”

“The Yanai Prize is the most important prize awarded at the Technion for excellence in teaching,” said the chairperson of the prize committee, Technion Executive Vice President for Academic Affairs Prof. Hagit Attiya. “It is also the most significant prize that the Technion awards to its faculty members. This clearly and concretely demonstrates the importance that the Technion attaches to teaching.”

Professor Sima Yaron spoke on behalf of the prize recipients. “Although I come from an engineering faculty, I believe that there is no one single formula for effective teaching, and there is no one single correct way to create a meaningful learning experience,” she said. “It’s very easy for me to remember three teachers that I consider teachers of life: teachers whose teaching method attracted me to mathematics and science in childhood, and a larger number of lecturers who taught me as a student, here at the Technion.”

Professor Yaron spoke about the extensive project initiated by students from the faculty in the wake of the oil spill incident in the southern Arava in December 2014.  A large group of students, accompanied by Technion faculty members, volunteered to research ways to remove pollution from the soil. “I always knew that we had a gold mine of wonderful students here,” said Professor Yaron, “but in that formative year, I learned that our students, even those who come late to class or unprepared to exams, or don’t do their homework, are just waiting for a trigger that will send them in the right direction. When that happens, they get carried away and devote themselves to the learning and work experience.”

The faculty prize went to the Faculty of Food Engineering and Biotechnology. “The prize fills me with pride, but doesn’t surprise me,” said Prof. Marcelle Machluf, Dean of the Faculty. “This is the result of many years of effort by faculty members and employees.  In selecting faculty members, we take into account not only the level of research but also excellence in teaching. Previous Yanai Prize winners from the faculty, Prof. Ayelet Fishman and Prof. Ester H. Segal, are joined this year by Prof. Sima Yaron, and I am sure she will not be the last. I thank the students at the faculty, who are the source of our success.”

Technion Student Union Chairman Omer Amit said that it is important to remember that the term “research university” includes not only the word “research” but also the word “university,” whose purpose is teaching. “You, the prize recipients, have now received a badge of excellence that bears a great responsibility: to be teaching ambassadors at your faculties and to inspire those lecturers that do not take teaching as seriously as you do.”

The Yanai educational initiative grant was awarded to the vertical-thematic studio which was established at the Faculty of Architecture and Town Planning. “The studio was established as part of the restructuring of teaching at the Faculty, and aims to link research to practice, to enrich the range of options available to students and to better prepare them for their final project,” explained studio founder Prof. Alona Nitzan-Shiftan.

The event was hosted by Prof. Ayelet Baram-Tsabari from the Faculty of Education in Science & Technology.

About the Yanai Prize

Moshe Yanai is a global pioneer in the field of information storage. His donation to Technion in the form of the Yanai Prize expresses his gratitude to Technion for the life skills he gained during his studies at the institute 40 years ago. Since he recalls the years of study at the university with hardship and periods of difficulty, he decided together with Technion President, Prof. Peretz Lavie, to contribute $12 million to award lecturers who have demonstrated teaching excellence, a gift that also greatly benefits Technion students. The prize, which awards NIS 100,000 to each lecturer, will be awarded over a period of 20 years.

For photos from the awards ceremony,click here

Photos:

1. Yanai2017 – Group photo of the Yanai prizewinners for 2017
2. 626 – Left to right: Dr. Lina Lavie, Moshe Yanai, Professor Peretz Lavie, Rachel Yanai, Professor Boaz Golani
3. 804 – Associate Professor Yoed Tsur from the Faculty of Chemical Engineering receives a teaching commendation
4. 164 – Professor Dan Ritter from the Faculty of Electrical Engineering receives a teaching commendation
5. 163 – Yanai Prize awarded at the Faculty of Food Engineering and Biotechnology. Left to right: Technion Executive Vice President for Academic Affairs Professor Hagit Attiya, Moshe Yanai, Student Union Chairman Omer Amit, Technion President Professor Peretz Lavie, and Dean of the Faculty Professor Marcelle Machluf
6. 022 – Assistant Professor Oded Amir receives the Yanai Prize
7. 341 – Assistant Professor Guy Bartal receives the Yanai Prize
8. 471 – Professor Eli Boehm receives the Yanai Prize
9. 156 – Professor Ron Holzman receives the Yanai Prize
10. 295 – Professor Sima Yaron receives the Yanai Prize
11. 995 – Professor Alona Nitzan-Shiftan and Faculty Dean Professor Iris Aravot receive the educational initiative grant for the establishment of the vertical-thematic studio at the Faculty of Architecture and Urban Planning

Photo: Nitzan Zohar, Office of the Spokesperson, the Technion