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IntroducingNew Scientists2014-2015

Introducing New Scientists 2014-2015

Table of contents

5 INTRODUCTION

Welcomingournewscientists

6 DEPARTMENT OF ORGANIC CHEMISTRY

Dr.AmnonBar-Shir Scienceinvividdetail

10 DEPARTMENT OF PARTICLE PHYSICS AND ASTROPHYSICS

Dr.KfirBlum Particularaboutparticles

14 DEPARTMENT OF PHYSICS OF COMPLEX SYSTEMS

Dr.EfraimEfrati Thescienceofnano-design

18 DEPARTMENT OF PHYSICS OF COMPLEX SYSTEMS

Dr.OferFirstenberg Quantumleap

22 DEPARTMENT OF STRUCTURAL BIOLOGY Dr.HagenHofmann Proteins,thelanguageofgenes

26 DEPARTMENT OF IMMUNOLOGY

Dr.YifatMerbl Aftertranslation

30 DEPARTMENT OF BIOLOGICAL CHEMISTRY

Dr.NetaRegev-Rudzki Solvingmalaria

34 Newscientistfundsandgifts

Introducing New Scientists 2014-2015 is published by

the Department of Resource Development

at the Weizmann Institute of Science

P.O. Box 26, Rehovot, Israel 76100

Tel: 972 8 934 4582

e-mail: resource.development@weizmann.ac.il

Design and production: Dina Shoham Design

Photography: Itai Belson and Ohad Herches

of the Weizmann Institute Photo lab

5

INTRODUCTION

Welcoming our new scientistsWe have hired seven extremely talented

young scientists so far this year. As is

well known, the market for top scientific

talent is global and highly competitive.

The best way we can compete at the

highest level is not only by providing a

fully equipped lab with all the tools and

support needed to go beyond the limits of

current knowledge, but also by offering

our scientists the freedom to explore any

new area of science that intrigues them.

The scientists we hire infuse the

Institute with new ideas and research

avenues, bring with them their

professional networks from their postdoc

labs abroad, and more. It is our highest

priority to fill our ranks with the very

best scientific minds, so that we ensure

the continuity of research and the

maintenance of the highest standards

of excellence for which the Weizmann

Institute is known. We compete with the

world’s best institutions, and we have

been highly successful in recruiting the

very best talent because we do not make

compromises.

Both through the investigations they

conduct in their labs and through their

education of the next generation of

Israeli scientists, these young researchers

are major drivers of Israel’s strength in

science and technology.

Our supporters around the world help

create the financial foundations that

enable these young people to come to

the Weizmann Institute, to build robust

labs, and to establish lifelong careers

at the Institute. We are grateful for this

generosity.

Please join me in welcoming our new

scientists to the Weizmann Institute.

Prof. Daniel Zajfman

President, Weizmann Institute of Science

6 7

Dr. Amnon Bar-ShirDr. Amnon Bar-Shir served as a paratrooper in the Israel Defense

Forces. He earned a BSc in chemistry in 2002 and an MSc in

chemistry in 2004, both magna cum laude at Tel Aviv University,

where he also completed his PhD in chemistry in 2009. He

worked as a postdoctoral fellow at the Johns Hopkins University

School of Medicine in Baltimore, Maryland, from 2009 until

joining the Department of Organic Chemistry in 2014.

His honors include the International Society for Magnetic

Resonance in Medicine (ISMRM) 2014 Junior Fellowship, three

summa cum laude Merit Awards of the ISMRM in 2014, 2013,

and 2012 and the magna cum laude Merit Award in 2013, two

first-place poster awards and a travel award for the 2013 World

Molecular Imaging Conference, a Maryland Stem Cell Research

Fund fellowship in 2012, the Joshua Jortner Prize of the Israeli

Chemical Society for outstanding PhD students in 2009, and a

number of student travel fellowships and awards. He is a member

of the International Society for Magnetic Resonance in Medicine

and the World Molecular Imaging Society.

Dr. Bar-Shir is married and has two children.

8 9

and without the limitations of X-ray or

nuclear-based imaging methodologies.

Scientists have been improving MRI

capabilities through the development

of innovative contrast agents that

provide specific details of physiological

changes, and through biosensors to tag

molecules of interest and view them

inside living cells.

Dr. Bar-Shir has already designed

a novel human-gene-based reporter

that generates high MRI contrast using

newly developed techniques. He is also

exploring the possibility of using MRI to

monitor changes in levels of metal ions,

which play a crucial role in a myriad of

biological processes.

As a graduate student, Dr. Bar-Shir

first became intrigued with magnetic

resonance as a tool to understand

structural changes in neuronal tissues

such as those occurring during the

progression of many neurological

disorders including multiple sclerosis

(MS), a disease of the central nervous

system. MS specialists use MRI scans as

a diagnostic tool to evaluate the loss

of the protective myelin sheathing and

other changes in the nervous system of

MS patients. As a PhD student, Dr. Bar-

Shir worked on a number of experimental

projects to refine the ability of magnetic

resonance to accurately show the

structural changes in nerve axons which

are associated with many neurological

disorders including MS.

Then, in his postdoctoral research,

Dr. Bar-Shir began working with an

innovative approach for generating MRI

contrast for studying the expression

of genes in vivo which may be used,

for example, to investigate the activity

of certain enzymes in a live subject. By

using an MRI technique called chemical

exchange saturation transfer (CEST),

multiple targets can be detected

simultaneously from the same region

of interest.

Modified genes can also serve as

‘reporters’ in MRI to probe changes in

gene expression and other changes in

the cell. Dr. Bar-Shir was part of a team

DR. AMNON BAR SHIR DEPARTMENT OF ORGANIC CHEMISTRY

Science in vivid detailSophisticated biosensors are literally bringing to light intricacies of biological function in health and disease

Genetically engineered biosensors,

nicknamed ‘reporter genes,’ are expected

to revolutionize the life sciences because

they dramatically improve the ability

of scientists and clinicians to monitor

the complex dynamics of biological

processes—such as gene expression, and

disease onset and progression—in real

time. Biosensors include proteins that

glow brightly under fluorescent light

and bioluminescent ‘reporter systems’

that produce and emit visible light

from genetically engineered cells and

organisms.

Dr. Amnon Bar-Shir, who joined the

Department of Organic Chemistry in

2014, aims to design the next generation

of biosensors used in conjunction with

magnetic resonance imaging (MRI) and

other contrast agents. By combining

synthetic chemistry and molecular biology

techniques, he intends to develop new

platforms for molecular and cellular MR

imaging applications.

MRI is one of the most powerful and

widely used biomedical tools in both

scientific research and medicine because

of its ability to create three-dimensional

high-resolution images of living

organisms. And it does so non-invasively

Biosensors have become the highlighters of modern biology, bringing into clear focus the processes and biology of the human body. Engineered by scientists, these light-emitting sensors stand out in striking contrast to their surroundings, showing their location in living cells and tissues in colorful relief.

that showed how to transform a gene

from a common herpes simplex virus into

an MRI reporter gene. This method and

its concept may help design new reporter

genes for in vivo imaging of a wide range

of targets.

In his new lab at the Weizmann

Institute, Dr. Bar-Shir plans to design

and synthesize wide range biosensors

for monitoring the expression of a gene

of the fruit fly, a much-studied genetic

model, and create a new kind of reporter

gene for MRI applications. By modifying

the substrate of this common enzyme, it

will be highly visible in MRI scans and also

have fluorescent properties.

As a test case, he plans to optimize the

reporter enzyme and use it to track the

viability of transplanted therapeutic cells

used in cell therapy.

10 11

Dr. Kfir BlumDr. Kfir Blum completed a combined BSc in physics and

electronics with honors at Tel Aviv University in 2004.

He received his MSc and PhD in physics at the Weizmann

Institute in 2007 and 2011. He then was a postdoctoral

fellow in the theoretical physics and astrophysics

departments in the School of Natural Sciences of the

Institute for Advanced Study at Princeton University.

Dr. Blum joins the Weizmann Institute in 2015.

He was awarded the Dean’s Excellence Prize in physics

at Tel Aviv University in 2003 and 2004, and the Dean’s

Prize in physics at the Weizmann Institute in 2007. In

2009 he received the Ze’ev Frankel Prize of the Israel

Physical Society, and in 2010 he received the Clore Israel

Scholarship Award.

12 13

DR. KFIR BLUM DEPARTMENT OF PARTICLE PHYSICS AND ASTROPHYSICS

Particular about particlesThe Higgs boson discovery solves some cosmic questions, but raises many more

Dr. Kfir Blum’s research spans a wide range

of topics in theoretical particle physics,

high-energy astrophysics and cosmology,

including studies of the Higgs boson

recently discovered at the Large Hadron

Collider; high energy Galactic cosmic rays;

neutrino physics; and the growth and

evolution of cosmic structure.

All of these topics pose profound

unsolved questions that affect our

understanding of the universe we live in,

from the smallest sub-nuclear quantum

world to the universe as a whole. The

weak scale hierarchy problem; the nature

of dark matter; cosmic matter—antimatter

asymmetry; the evolution of cosmological

structure in the early physical world; the

origin of cosmic rays—all these questions

are often intertwined, Dr. Blum says. One

of his main areas of research concerns

the attempt to find a solution to the so-

called “weak scale hierarchy problem” by

studying the physics of the Higgs boson at

the Large Hadron Collider (LHC) at CERN.

The discovery of the Higgs particle

at the LHC in 2012 marks a major

achievement for particle physics. The

Higgs particle was posited five decades

ago. Subsequent precision measurements

of the scattering of electroweak gauge

bosons suggested indirectly that a Higgs

particle with mass of the order of 100 GeV

(a hundred times heavier than the proton)

was needed to explain the experimental

results. Alternative, more complicated

possibilities (including the absence of

a Higgs particle) were still conceivable

until 2012. The LHC discovery of a 125

GeV Higgs boson settled the debate in

favor of simplicity.

But finding the Higgs boson at the

LHC did not just settle a long-standing

puzzle. It also opened the door to a

deep and subtle question that sits at

the heart of our understanding of the

electroweak force interactions, and more

generally of quantum field theory as

a whole. The problem is that while the

Higgs mechanism with a Higgs particle

provides a consistent description of the

electroweak interactions, this description

appears to comprise an incredibly fragile

structure. This “fragility” is known as the

weak scale hierarchy problem, and its root

is in the mass of the Higgs particle itself.

Our understanding of quantum field

theory tells us that the Higgs mass

should be dictated by short-range—or

high energy—phenomena. In practice this

means that whenever scientists attempt

to add new particles or new forces to

the currently known list, they end up

predicting a large correction to the Higgs

mass, in conflict with observations. If

there were no new particles or forces to

be added, this would not be a problem.

However, physicists suspect that, indeed,

such new particles and forces exist, as

there are several phenomena in the

universe that the Standard Model falls

short of describing.

Arguably, the first such phenomenon

is gravity. The distance range at which,

it is believed, gravity comes to dominate

the interactions of particles is very short.

But if this were correct, then the resulting

value for the Higgs mass would have

been 34 orders of magnitude above the

experimentally measured result—posing

a fundamental theoretical inconsistency.

There are other shortcomings of

the Standard Model that require new

particles or forces, which pose a fine-

tuning problem for the Higgs mass. These

shortcomings include the finite mass

of the neutrino, the cosmic asymmetry

between matter and antimatter in the

universe, and dark matter.

Future measurements of the

interactions of the Higgs particle at

the LHC promise to refine and improve

current knowledge. Dr. Blum studies the

theoretical aspects of this research.

Dr. Blum’s studies of Higgs physics so

far suggest that if ever a modification

to the interactions of the Higgs boson

will be detected at the LHC, violating the

Standard Model predictions, then this will

be sufficient to conclude that new bosonic

particles do indeed exist. Experimental

indication of any distortion in the Higgs

interactions would thus be a promising

hint that can put scientists on the right

track to solving one of the most subtle

outstanding questions of our time,

Dr. Blum says.

Whenever scientists attempt to add new particles or forces to the currently known list, they end up predicting a large correction to the Higgs mass

14 15

Dr. Efraim EfratiDr. Efi Efrati received a BSc in physics and mathematics magna

cum laude (2003), and an MSc (2005) and a PhD (2010) in physics

summa cum laude, all from the Hebrew University of Jerusalem.

He was a postdoctoral scholar at the University of Chicago from

2010-2013, and joined the Department of Physics of Complex

Systems at the Weizmann Institute of Science in 2014.

Dr. Efrati has been awarded a number of academic honors,

including the Simons Postdoctoral Fellowship at the University of

Chicago (2010-2013), and the Hebrew University of Jerusalem Max

Schlomiuk Award for Outstanding PhD Thesis (2011), the Giulio

Racah Prize for theoretical physics (2004) and faculty of math and

science scholarships for excelling students from 2003 to 2005.

Dr. Efrati is married and has two children.

16 17

For physicists like Dr. Efraim (Efi) Efrati, frustration is not an emotional condition to be avoided.

DR. EFRAIM EFRATI DEPARTMENT OF PHYSICS OF COMPLEX SYSTEMS

The science of nano-design

Frustration, to physicists, is a

physical state that may be the basis

to understanding a host of puzzling

phenomena that affect a variety of

systems from molecular self-assembly

to the ruffling of the edge of a growing

daffodil, or plastic flow in ductile

materials. In short, it may explain a great

deal about why the living and non-living

things we take for granted all around

us—from grass and asphalt to hair and

fabric—look the way they do.

The components of these physical

systems are endowed with “contradictory

tendencies” that cannot all be

simultaneously reconciled, thus making

them “frustrated.” It is the competition

between these contradicting tendencies

that allows simple building blocks of

various materials to assemble into

sophisticated objects displaying elaborate

structures and exhibiting exotic responses.

A simple example of a frustrated system

is a collection of three atoms, each seeking

to connect to the other two atoms to form

a triangle (180 degrees). However, the

structural nature of many atoms is such

that they do not allow for the formation

of 60-degree angles to form the triangle.

Instead, the atom’s 70 or 80 degree

angle vertex, for instance, prevents—read:

frustrates—the creation of the triangle.

How can such frustration be resolved?

This is the subject of Dr. Efrati’s work.

More specifically, his research

focuses on the interplay between local

and global effects in frustrated elastic

systems, self-assembling systems, and

systems of statistical mechanics. Often,

this frustration may be resolved locally;

in the example above this is achieved

by compromising all the vertex angles

equally. However, in some cases, such

as the two examples shown here,

the form and function of the assembled

object depend on global properties

characterizing the body as a whole, such

as its spatial dimensions.

The ruffled edge of a daffodil in is a

phenomenon exhibited by frustrated

systems—but a quantitative description of

the underlying mechanisms still mystifies

scientists. A fundamental understanding

of these mechanisms will enable scientists

to discern quantitative rules that could

lead to the design of new types of

materials with applications ranging

from cloaking meta-materials—artificial

materials engineered to have properties

that may not be found in nature to

render an object seemingly invisible—to

soft machines, which use soft materials

that can deform in response to stimuli

other than mechanical forces for making

machines and devices that work at the

nanoscale.

During his postdoctoral research,

Dr. Efrati also applied the tools from

the fields of differential geometry

and mechanics of frustrated systems

to improve surgical procedures. By

applying methods from his research,

Dr. Efrati helped establish new ways of

understanding the underlying geometry

of a bowel surgery devised to alleviate

Crohn’s disease symptoms. These

understandings can be used by non-

mathematicians and are expected to

have a profound impact on the design of

surgical instruments.

The starfish pattern observed in the self-

assembly of chiral rod-like viruses. Image

from Nature (2012).

Why do daffodils have ruffled edges? How can fine surgical instruments be more smartly built?

18 19

Dr. Ofer FirstenbergDr. Ofer Firstenberg completed his BSc summa cum laude

in physics in 2000 at the Hebrew University of Jerusalem

as part of the prestigious Talpiot program of the Ministry of

Defense. Dr. Firstenberg then obtained his MSc summa cum

laude (2006) and PhD (2010) in physics at the Technion—Israel

Institute of Technology while also working as head of a

quantum optics group and sub-department manager at Rafael

Advanced Defense Systems. In 2011 Dr. Firstenberg started

his postdoctoral training at the Harvard University Quantum

Optics Center, in cooperation with MIT’s Research Laboratory

of Electronics. Dr. Firstenberg joins Weizmann Institute of

Science in 2014.

His prizes include the Rector’s Prize (1998) and Dean’s

Award (1999) for undergraduate studies; the Katzir Scholarship

for scholastic excellence and leadership potential (2006); the

Israel Physical Society Prize in experimental physics (2009);

the Rothschild Fellowship (2011); the Fulbright Postdoctoral

Fellowship (2011); and the Harvard Quantum-Optics Center

Postdoctoral Fellowship (2011). He is the recipient of the 2014

Clore Prize for Outstanding Appointment as Senior Scientist

at the Weizmann Institute.

Dr. Firstenberg is married and has two children.

20 21

harnessed for quantum computations.

In his new lab at the Weizmann Institute,

Dr. Firstenberg will advance his research

on quantum non-linear optics, including the

study of photonic crystalline and correlated

liquid phases, as well as highly entangled

states of light. In addition, he intends to

further develop the theory of quantum non-

linear optics—for example, the extension

of theory into multiple dimensions—and

improve experimental techniques that

will provide higher interaction strengths

between photons.

DR. OFER FIRSTENBERG DEPARTMENT OF PHYSICS OF COMPLEX SYSTEMS

It has been acknowledged that the

computational power of electronic

computers is finite, thus limiting current-

day computers’ capacity to overcome

complex cryptography and massive

computations.

One of the proposed solutions for this

is the use of quantum computers, which

process information carried by light

photons and potentially have much more

computational power. Yet a major hurdle

exists in quantum computing: It requires

the manipulation and control of photons

carrying the data, which is currently

impossible on a commercial scale.

Dr. Ofer Firstenberg studies quantum

non-linear optics—the way in which

quantum information is carried and

manipulated by photons and atoms. His

training in this field comes from industry

as well as academia, having worked as

head of a quantum optics group and sub-

department manager at Israel’s Rafael

Advanced Defense Systems.

Quantum leap

Since the computer was invented, computer technology has seen many developments and improvements that would have made its pioneers gasp.

New advances in quantum non-linear optics, towards a new computer age

In a recent study as a postdoctoral

fellow at Harvard University’s Quantum

Optics Center, Dr. Firstenberg was part

of a team that succeeded in coupling two

photons in a bond which resembles a

molecule by using cold Rubidium atoms as

a medium. This is a form of matter which

was never previously witnessed, and until

recently was claimed to be theoretically

impossible. The findings imply that

under certain conditions, photons—which

are considered massless—behave like

regular matter, thus allowing them to be

Photons with strong mutual attraction

in a quantum nonlinear medium.

Credit: O. Firstenberg, et al.

22 23

Dr. Hagen HofmannDr. Hagen Hofmann was born in Sangerhausen, Germany.

He completed an MS in biochemistry with distinction at

Martin Luther University in Halle-Wittenberg, Germany,

in 2004 and received his PhD summa cum laude in

biochemistry in 2008 from the same institution. In 2006,

he visited the Weizmann Institute as a research fellow in

the lab of Prof. Gilad Haran in the Department of Chemical

Physics. Dr. Hofmann was a postdoctoral fellow at the

University of Zurich, Switzerland, from 2008 until joining

the Department of Structural Biology at the Weizmann

Institute of Science in 2014.

His academic and professional awards include

scholarships from the German National Academic

Foundation and a Max Buchner Research Grant from

the DECHEMA (Society for Chemical Engineering and

Biotechnology).

He is married and has two children.

24 25

DR. HAGEN HOFMANN DEPARTMENT OF STRUCTURAL BIOLOGY

Proteins, the language of genes

Tiny man-made “microfluidic” devices can isolate single cells for observation under powerful microscopes

Studying their creation from the bottom up

Scientists can now use techniques

such as single-molecule fluorescence

spectroscopy to zoom in on specific

molecules within single living cells.

Dr. Hagen Hofmann—who joined the

Weizmann Institute in 2014—plans to

use these cutting-edge tools to identify

the action of individual molecules in a

living cell. In his new lab, he will explore

what happens, step by step, in vital

processes such as the transcription of

genes and the production and folding

of proteins.

While biologists know a lot about the

overall process of how transcription

factors switch genes on and off, it has

been difficult to precisely predict the

dynamics of whole gene networks. Dr.

Hofmann hopes to close the gap between

the observed dynamics of cellular

circuits and their underlying molecular

mechanisms. His efforts will combine

tools and theories from molecular

biophysics and systems biology, drawing

on both theorists and experimentalists in

biology and physics.

As a postdoctoral fellow at the

University of Zurich, he worked with a

team of biochemists and physicists from

that institution and from the University

of California, Santa Barbara (UCSB) to

make single-molecule measurements of

an essential biological molecule known

as a chaperonin in reactions taking place

from less than a second up to hours.

Chaperonins act as guides or chaperones—

hence the name—within a cell to assist in

the folding of other proteins.

The scientists used microfluidic devices

built at UCSB and at the University of

Zurich to follow chaperonin reactions in

a channel one-tenth the size of a human

hair. Their experiments indicate that the

chaperonin slows the folding of their test

protein, allowing it to find the correct

folded shape while it is protected from

aggregation, the clumping together of

misfolded proteins. Further studies using

this new method may help to determine

whether the failure of chaperonins could

be responsible for pathogenic aggregation

of proteins that are thought to contribute

to neurodegenerative diseases such as

Alzheimer’s and Parkinson’s.

In his new lab at the Weizmann

Institute, Dr. Hofmann wants to work

from “the bottom up,” he says, starting

at the molecular level, observing and

measuring single DNA-binding events of

transcription factors in vitro using single-

molecule fluorescence spectroscopy.

Then he will move to the cellular level,

using single-molecule live-cell imaging to

measure the number and distribution of

the transcription factors. He plans to start

with a challenging pair of transcription

factors found in simple bacteria. By

understanding how each factor works,

he hopes to understand how all the

different components of a regulatory

genetic circuit interact.

26 27

Dr. Yifat MerblDr. Yifat Merbl completed her BSc summa cum laude

in computational biology at Bar-Ilan University in

2003. She earned an MSc in immunology at the

Weizmann Institute in 2005 under the guidance of

Prof. Irun Cohen. She joined the first PhD program

in systems biology at Harvard Medical School,

completing her PhD there in 2010. She stayed on

at Harvard as a postdoctoral fellow until joining

the Department of Immunology at the Weizmann

Institute in 2014.

During her student years in Israel, Dr. Merbl also

worked as a research and development assistant

at Optimata Ltd. in Ramat Gan, and as a research

assistant at the Institute for Medical BioMathematics

(IMBM) in Bene Atarot. She is the author of two

patents, including one for the application of her

protein profiling system to clinical diagnostics and

biomarker discovery.

She was selected for the NIH Independent Award

in 2010. She received a pre-doctoral fellowship in the

Department of Systems Biology at Harvard Medical

School, the Center for Complexity Science Award

in 2005, the Sarah Werch Research Scholarship

in 2004, and the Sara Rottenberg Scholarship in

Cancer Research at the Weizmann Institute in 2003.

She received the 2000 President’s Excellence Award

at Bar-Ilan University. In 2014, she was also selected

to join the Israeli Centers of Research Excellence

(I-CORE) program in structural biology of the cell.

28 29

DR. YIFAT MERBL DEPARTMENT OF IMMUNOLOGY

While a gene encodes the directions

to make a single protein, the final

form of the protein varies due to post-

translational modifications (PTMs) —

changes that occur after building the

exact sequence of amino acids — that tell

a protein whether to be active or silent,

where to go in the cell, and when to

report to the cellular recycling center

for disposal.

Because of these post-translational

changes, there are estimated to be about

three orders of magnitude more diverse

forms of proteins than the number of

genes.

Dr. Yifat Merbl, who joined the

Weizmann Institute of Science in 2014

after a postdoctoral fellowship at Harvard

University, is fascinated by the complexity

that PTMs add to biological systems

and is interested in understanding the

principles that govern how they work.

Dr. Merbl envisions the vital information

that could be generated if one could take

After translation

Dr. Merbl used the profiling system she developed to study one of the most important post-translation modifiers, ubiquitin, in the process of cell division.

Understanding changes to proteins post-translation

a snapshot or fingerprint of the global

changes in protein modifications at a

specific moment in a cell, such as during

the development of cancer. However, to

study post-translational modifications in

greater numbers, she had to develop a

new system to analyze them.

Drawing on her background in

computational biology, cell biology,

biochemistry and immunology, Dr. Merbl

developed a high-throughput system

that enabled her to monitor post-

translational modifications of thousands

of proteins in parallel, under conditions

relatively close to those of the complex

cellular environment. The challenge

was to integrate the strength of classic

biochemical approaches, analyzing one

protein at a time, with new technology’s

ability to systematically monitor changes

in a global manner. She developed

a profiling system using protein

microarrays that allow her to identify

the changes that occur to thousands of

individual proteins, simultaneously.

Dr. Merbl used the profiling system

she developed to study one of the most

important post-translation modifiers,

ubiquitin, in the process of cell division.

Israeli scientists Profs. Aaron Ciechanover

and Avram Hershko shared a Nobel Prize

in Chemistry in 2004 for showing how

ubiquitin affects thousands of proteins

in fundamental cellular processes and

tags proteins for degradation in the

cellular recycling system. Dr. Merbl has

continued to explore the roles of other

members of the ubiquitin family which

are poorly studied and revealed a novel

mechanism of a ubiquitin-like protein

in controlling cell division. This protein,

called FAT10, is involved in the regulation

of a pathway that has been implicated in

the pathogenesis of cancer and in immune

system pathologies.

Dr. Merbl has tested the potential of

her system to generate novel insights

about the molecular basis of disease. As

proof of concept, she studied changes in

ubiquitin profiles between healthy

and diseased cerebrospinal fluid samples

in Alzheimer’s disease and from tissue

biopsies of cancer patients. The analysis

revealed correlations between specific

protein modifications and the diseased

state.

In her new lab at the Weizmann

Institute, Dr. Merbl wants to zero in on

how the ubiquitin system controls the

macrophages that have been shown to

play a role in various human disorders

ranging from inflammatory diseases (e.g.

rheumatoid arthritis and inflammatory

bowel disease) to cancer.

Schematic drawing of the high-throughput system

Dr. Merbl designed for post-translation modification

profiling and profiles of ubiquitin family members

and their targets in mitosis. From Cell 2013

30 31

Dr. Neta Regev-Rudzki Dr. Neta Regev-Rudzki served as an officer in a tank unit during

her military service. She completed a BSc in chemistry (1999), an

MSc in biochemistry (2002), and a PhD in microbiology and cell

biology (2009), all at the Hebrew University in Jerusalem. During

a subsequent postdoctoral fellowship at the Walter and Eliza Hall

Institute of Medical Research (WEHI) in Melbourne, Australia, she

became interested in parasitology and turned her attention to

malaria. She joined the faculty of the Department of Biological

Chemistry at the Weizmann Institute in 2014.

Her academic and professional honors include an Early Career

Fellowship (2012) from Australia’s National Health and Medical

Research Council, a Rothschild Post-Doctoral Fellowship (2010), and

a Prize from the Israel Society for Microbiology for an outstanding

PhD thesis. She was one of the top young scientists invited to the

57th Lindau Nobel Laureate Meetings in Germany (2007). Dr. Regev-

Rudzki was honored with distinction as an outstanding instructor

at Hadassah College in Jerusalem. She won the 2006 Aharon

Katchalsky-Katzir Travel Fellowship at the Weizmann Institute, the

2004 and 2005 prizes for outstanding teaching instructor in the

medical faculty of the Hebrew University, the 2001 National Israel

Knesset Prize for Outstanding BSc Students, and the 2001 Hebrew

University Rector’s BSc Prize.

Dr. Regev-Rudzki is married and has three children.

32 33

DR. NETTA REGEV-RUDZKI DEPARTMENT OF BIOLOGICAL CHEMISTRY

Solving malaria

Every year, hundreds of millions of people are infected with the malaria parasite, and about 700,000 die. The parasite, Plasmodium falciparum, is a major killer in developing countries and is especially deadly for small children and pregnant women.

Paradigm-shifting insights on how malaria spreads in the blood

The parasite’s resistance to available

drugs is a major obstacle and today no

effective vaccine exists.

The malaria parasite is transmitted to

humans through mosquito bites.

It then spends an incubation period in the

bloodstream — the “blood stage”— which

leads to the disease in humans. At this

stage, it can be activated into the sexual

form (gametocytes) that gives it the best

chance of being transmitted back to the

mosquito to continue its life cycle.

As a postdoctoral fellow at Walter and

Eliza Hall Institute of Medical Research

(WEHI) in Melbourne, Australia,

Dr. Neta Regev-Rudzki and her colleagues

showed in an unprecedented study that

P. falciparum-infected red blood cells

communicate by releasing tiny, sac-like

nanovesicles. These contain little packets

of DNA that carry information from one

parasite to another. It appears that this

mechanism indicates to the malaria

parasite how many other parasites are

present in the human and affects the

timing of its activation into gametocytes.

It was such a startling discovery that

the team repeated the experiments

many times in many different ways

before they really started to believe that

these parasites were signaling to each

other and communicating. Dr. Regev-

Rudzki’s discovery has fundamentally

changed the research world’s view

of the malaria parasite and is a leap

forward in understanding its survival and

transmittal. The next step is to identify

the molecules involved in this signaling

process, and ways that could block these

communication networks to disrupt the

transmission of malaria from the human

to the mosquito.

Dr. Regev-Rudzki also identified

a P. falciparum-exported protein,

PfPTP2, which plays a key role in the

communication process. She was able to

locate it inside the cell and observe its

action using super-resolution microscopy

and immunoelectron microscopy.

Her results strongly suggest that PfPTP2

functions in the process of the budding

of the vesicles, and it appears to be

one critical step in the communication

process.

In her new lab at the Weizmann

Institute, Dr. Regev-Rudzki plans to

delve deeper into the signaling pathways

in the biology of the parasite and look

for potential targets to block their

replication. Approaching the problem

from a genetic perspective, she plans

to take a broad approach to identify the

genes and RNAs that are involved. One

of her first challenges will be to isolate

and purify the nanovesicles that carry the

DNA-encoded messages, which she has

already shown can convey resistance to

malaria drugs.

The next step will be to identify the

proteins associated with the nanovesicles

and analyze their functions. She suspects

the nanovesicles contain microRNA

and noncoding RNA (ncRNA) molecules

that also transfer signals to recipient

cells. She plans to identify these RNA

molecules to determine if they are also

involved in cell-cell communication.

34 35

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