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发帖数: 20445 | 1 A-D E-K L-P R-Z
Peter Baumann, Ph.D.
HHMI Early Career Scientist
Stowers Institute for Medical Research
Peter Baumann’s research focuses on beginnings and endings: beginnings in
the form of reproduction in unisexual lizards and endings in the form of the
telomeres that protect chromosome tips.
Each time chromosomes are copied, telomeres—specialized stretches of DNA
that extend from the ends of each chromosome—become progressively shorter.
With each cell division, they erode further until cells are no longer
capable of dividing and stop growing. An enzyme complex known as telomerase
can lengthen telomeres by adding DNA using a dedicated RNA subunit as
template. As a postdoctoral researcher, Baumann discovered a protein he
named POT1 that binds to telomeres, protects them, and regulates telomerase
activity. That regulation is critical, as shortening telomeres are
associated with aging, but too much telomerase can lead to cancer. Today,
Baumann continues to investigate the molecular and genetic mechanisms of
telomere protection and lengthening. His work has identified the RNA
component of telomerase in yeast and has helped explain how the enzyme is
assembled from its components; his team is now expanding these studies to
human telomerase.
Baumann also studies unisexual whiptail lizard species, in which the females
can reproduce and thrive without a mate. He revealed how females can
produce offspring without males and how they maintain a healthy genetic mix
without the continuous reshuffling of genes from males and females. A goal
of that research is to understand the molecular underpinnings of asexual
reproduction, an endeavor that will inform agricultural research on how to
harness desirable traits in unisexual lineages and expand our understanding
of vertebrate evolution.
Michael S. Brainard, Ph.D.
University of California, San Francisco
Michael Brainard’s fascination with how the brain learns led him to the
songs of birds. Songbirds and humans are rare experts at vocal learning, he
explains, and birds offer an ideal model system for studying how this
learning occurs. Brainard has been studying young male Bengalese finches,
which learn their signature melody by trying to mimic the memorized song of
their fathers, warbling the tune over and over until they get it right. In a
series of creative experiments, Brainard showed that a group of structures
deep in the brain, the basal ganglia, is crucial: It provides corrective
feedback when birds hit wrong notes.
When Brainard blocked the signal coming from basal ganglia, however, he made
a surprising discovery. Block the feedback signal and a bird doesn’t
appear to learn, as expected. But unblock the signal and the bird
immediately hits many more correct notes. The results show that the basal
ganglia can “covertly” learn even when feedback is cut off.
Brainard is expanding his research to investigate what changes occur in the
brain with aging that limit the adult bird’s ability to learn. And he’s
planning genetic and inheritance studies to understand why some finches
learn well while others learn poorly.
Jean-Laurent Casanova, M.D., Ph.D.
Rockefeller University
Jean-Laurent Casanova champions an unorthodox explanation for why some
children fall ill with serious infections while their playmates remain
healthy. Some apparently healthy children, he argues, were born with genetic
mutations that sap the immune system’s ability to fend off a specific
microbe.
Researchers had thought that these inherited immune impairments were rare
and would undermine the body’s defenses against a variety of pathogens, as
seen in patients with acquired immunodeficiencies, such as AIDS. But over
the past 15 years, Casanova, a geneticist and trained pediatrician, and his
collaborators worldwide have documented several examples of genetic glitches
that leave some children vulnerable to particular pathogens. Their research
has dissected the molecular malfunctions responsible. For example, herpes
simplex virus-1 (HSV-1) usually causes nothing worse than cold sores in most
children. But the same virus can spark a life-threatening brain illness (
encephalitis) in others. Casanova’s team has shown that children with HSV-1
encephalitis carry gene mutations that hamper the production of virus-
fighting molecules called interferons in the brain.
Casanova and his colleagues have made similar discoveries for tuberculosis,
various fungal and bacterial diseases, and other infectious illnesses.
Children are already benefitting from Casanova’s unconventional perspective
. His work suggested a new way to treat infections—using recombinant
molecules missing in the sick child resulting from a mutation—to boost the
immune response to the invading microbe. He hopes that digging up novel
vulnerabilities in our genes might help in devising ways to treat the
pathogens that exploit them.
Adam E. Cohen, Ph.D.
Harvard University
Instead of prodding neurons with electrodes to measure their electrical
activity, researchers can now watch as the cells fire off impulses, thanks
to Adam Cohen. For a neuron to fire, inputs from neighboring cells must push
the neuron’s membrane potential (a difference in voltage between the
interior and exterior of the cell) above a certain threshold. Cohen and his
colleagues rejiggered a light-sensitive protein from a microbe that inhabits
the Dead Sea so that the protein flashes in response to changes in a cell's
voltage. The researchers can genetically engineer cells to carry this
protein and then use imaging to track cells that are firing.
Last year, the team put its genetically encoded fluorescent voltage
indicator protein into rat brain neurons to observe individual action
potentials, or nerve cell impulses. And Cohen's team is working to
illuminate other kinds of cells that are electrically active. They are
studying heart cells derived from patients who have potentially fatal
genetic disorders that can lead to an erratic heartbeat. They hope that the
pattern of flashes will reveal how heart cells fire abnormally. To learn how
the heart gets in rhythm during embryonic development, the team has
incorporated the protein into the heart cells of zebrafish.
Those applications might be just the beginning. After honing the technique,
Cohen foresees using the voltage sensor protein to scrutinize networks of
neurons as an animal learns, for instance, or to uncover how the developing
brain gains the ability to transmit electrical signals.
Karl Deisseroth, M.D., Ph.D.
HHMI Early Career Scientist
Stanford University
As a practicing psychiatrist, Karl Deisseroth experienced firsthand the
failure of drugs and other treatments to help many of his patients. So in
his Stanford research lab, he founded a revolutionary new field of
bioengineering and neuroscience, called optogenetics, for understanding and
targeting specific pathways in the brain.
Deisseroth's first major innovation was slipping a gene that produces a
light-sensitive protein from algae into neurons. Using a variety of proteins
, Deisseroth's team has shown that it can stimulate or inhibit neurons with
millisecond-precision flashes of light. By switching specific populations of
neurons in the brain on or off to observe effects on behavior, they have
obtained insights into the functions of neural circuits relevant to
Parkinson's disease, anxiety, substance abuse, depression, narcolepsy, and
autism. The approach, now being used in thousands of laboratories with which
Deisseroth has shared his tools, offers tremendous promise for
understanding normal circuitry, as well as aberrant brain circuits and
treatment mechanisms in diseases such as depression, Parkinson's, and
epilepsy.
And it's been made even more powerful by Deisseroth's latest achievement,
CLARITY—a method of stripping the brain of its fat so that neural circuits
can be seen and investigated with unprecedented clarity and completeness.
Having built, applied, and distributed these revolutionary tools, Deisseroth
is now setting his sights on new challenges, including developing methods
to link circuit control with activity and structure of the same neural
circuit. If successful, such an integrated approach will further deepen our
understanding of neural systems and behavior in health and disease.
Michael A. Dyer, Ph.D.
HHMI Early Career Scientist
St. Jude Children's Research Hospital
Few researchers can say they have made a discovery that overturned a long-
held tenet of biological science. Yet early in his career, Michael Dyer has
already done so twice.
His studies of the eye's retina have contested a century-old dogma: that
mature, differentiated neurons can no longer divide and form new neurons.
Witnessing a mature neuron divide while maintaining its synaptic connections
was a transformative moment for Dyer—and a springboard for future
investigations.
In another landmark finding, Dyer discovered that the early childhood eye
tumor, retinoblastoma, is a striking counterexample to the textbook account
of how cancers develop: that is, through years or decades of DNA-changing
mutations that ultimately turn cells malignant. He showed that a single
mutation in the Rb protein alters the turning off and on of numerous genes
throughout the genome without altering DNA itself. This is called an
epigenetic mechanism.
Following up on these discoveries has led Dyer to propose that every nerve
cell has its own degree of pliancy—a property that is established early in
development and determines how susceptible the cell is to degeneration or
cancer. Cells that are resistant to degeneration may be more likely to
become cancerous, and vice versa. Dyer has developed tools to measure
cellular pliancy, and intends to explore its molecular underpinnings and how
it contributes to normal nerve development, cancer, and neurodegenerative
diseases. | p*****c
发帖数: 20445 | 2 Marc R. Freeman, Ph.D.
HHMI Early Career Scientist
University of Massachusetts Medical School
Neurons hog the attention, but our brains couldn’t operate without the
unassuming neural cells called glia. Marc Freeman is working to bring these
overlooked cells—which represent about 60 percent of brain cells—their
share of credit.
Freeman has been dissecting the role of glia in brain development, function,
and healing after injury, when glia hurry to the damaged area and devour
cellular debris to allow for brain recovery. Working on fruit flies, Freeman
and colleagues pieced together a complex circuit involving a damage-
stimulated protein called Draper and more than 20 molecules that mobilize
glia.
Freeman’s team is learning that the appetite of glial cells may prove
crucial in building brain circuitry—from wiring neurons in the brain to
establishing synapses, the junctions between nerve cells. They discovered
that glia slip into synapses under construction and remove cellular junk,
which is necessary for the growth of healthy synapses. They have also homed
in on a subtype of glial cells in the fly, called astrocytes, and found that
these cells help orchestrate the formation and function of synapses.
Freeman’s interest in the brain’s response to injury led to the
identification of a suicide mechanism in axons, the projections from neurons
that transmit messages to other cells. His lab found that injured axons
activate a program that drives their own destruction. Mutations in one gene
in this pathway result in severed axons surviving about 50 times as long
after injury. Freeman intends to probe this axon degeneration pathway more
deeply in hopes of identifying factors that help neurons survive or fend off
damage, with the ultimate goal of blocking this pathway to stop
neurodegenerative disease.
Chuan He, Ph.D.
University of Chicago
By bringing a chemist's perspective to biological problems, Chuan He has
made some surprising discoveries. His work has shed light on the roles of
metals in biological systems, identified bacterial regulators of virulence
and antibiotic resistance, illuminated mechanisms of DNA repair, and
revealed new modes of genetic regulation.
He now wants to understand how the addition and removal of methyl groups on
genetic material reversibly alter gene activity. Such modifications to DNA
are well known to influence how the genetic code is read, and in 2011, He's
group showed that reversible modifications to RNA can have similar effects.
He found that the most prevalent internal methylation on human messenger RNA
, methylation of the nucleoside adenosine, is reversible and could affect
protein levels in cells. His lab went on to demonstrate that two
functionally significant human proteins, FTO and ALKBH5, remove methyl
groups from RNA. He now plans to continue exploring the scope, mechanism,
and effects of reversible RNA methylation in biological regulation.
He's laboratory is also known for developing chemical technologies to label
and sequence a recently discovered chemical modification in DNA—5-
hydroxymethylcytosine, or 5hmC—that is particularly abundant in the brain.
Current research suggests that 5hmC is an intermediary molecule produced
when DNA is demethylated and it may directly impact gene activity in various
cells. He's tools made it possible to detect and survey the exact locations
of 5hmC as well as its further oxidized derivatives, such as 5-
formylcytosine, or 5fC, in the mammalian genome. He will continue to explore
their functional roles as well as the mechanism of demethylation.
Hopi Hoekstra, Ph.D.
Harvard University
Hopi Hoekstra doesn’t stay within the lines, at least not when it comes to
scientific disciplines. In her quest to understand the genetics of adaptive
evolution, she is doing research that spans cell and molecular biology,
ecology, behavior, genomics, evolutionary theory, and computational biology.
Hoekstra has taken deer mice—the most abundant mammal in North America and
one of the most well-studied ecologically—out of their natural setting and
into the lab. Using wild deer mice as a model system, she’s studying the
molecular basis of how adaptation to novel selective pressures generates and
maintains diversity in nature. She wants to understand every step of the
process, from DNA sequence changes to phenotypes to the ecological and
evolutionary significance of those phenotypes.
Her early work, in which she helped identify the molecular basis of melanism
(dark coloring) in lava-dwelling populations of rock pocket mice, was one
of the first examples of a specific gene influencing evolution by natural
selection. Then Hoekstra combined field and lab-based approaches to show how
individual and cumulative genetic changes in deer mice could cause fast,
dramatic variation in the animals’ morphology and reproduction, which
improved their ability to survive and reproduce in the wild. Some of her
latest research delves into the genetics and evolution of behavior: Hoekstra
identified specific regions of deer mouse DNA that are involved in how long
the mice’s burrows are and whether they contain an escape route. She is
now extending this approach to study exploratory and parental behaviors.
Such research sets the stage for future work, which she hopes will lead her
to a general understanding of the adaptive process—from the molecular to
the neurobiological to the organismal level.
Neil Hunter, Ph.D.
HHMI Early Career Scientist
University of California, Davis
Neil Hunter’s research is changing the way scientists think about how
chromosomes swap segments to shuffle their genes and repair DNA damage. The
process, known as homologous recombination, is critical for reproduction and
fuels evolution. When it fails, birth defects, miscarriage, and cancer can
result.
Homologous recombination occurs when a broken chromosome uses a second,
intact chromosome as the template for its repair. This process is critical
for repairing both intentional and accidental breaks in DNA. While
homologous recombination is essential for maintaining the integrity of the
genome, it can also introduce genetic diversity, which creates an
opportunity for new traits to evolve.
Hunter focuses on how homologous recombination proceeds and is regulated
during meiosis, the cell division process that produces sperm and eggs.
During meiosis, the chromosome complement is halved so that the normal
chromosome number is maintained after fertilization occurs, with each parent
contributing one full set of chromosomes. Homologous recombination creates
connections, called crossovers, between paternal–maternal chromosome pairs
that are essential for their distribution to sperm and egg cells. Defective
recombination results in sperm and eggs with the wrong number of chromosomes
, a situation that can cause pregnancy miscarriage and diseases such as Down
syndrome.
Hunter has developed innovative techniques to monitor the molecular steps of
recombination in budding yeast cells, and he has used them to identify
unexpected aspects of the process not revealed by conventional techniques.
His future studies will integrate yeast and mouse molecular genetics, high-
resolution imaging of chromosomes, biochemistry, and mathematical modeling
to continue to investigate the details of homologous recombination during
meiosis.
Akiko Iwasaki, Ph.D.
Yale University
"Good" bacteria in the gut do more than help digest food. They can also
boost the immune system in its fight against flu infections in the lungs.
That's one of the many surprising findings made by Akiko Iwasaki, whose
research straddles the fields of immunology, microbiology, and virology.
Iwasaki was the first to show the crucial role of dendritic cells in
recognizing certain DNA and RNA viruses. Dendritic cells are the watchdogs
of the immune system, patrolling skin and mucosal surfaces for foreign
invaders. She was the first to identify receptors that spot the virus, and
she revealed the importance of autophagy (a process in which cells destroy
unwanted material inside them) in responding to viral pathogens. She's even
created a new vaccination approach against viruses that attack through the
lining of the lungs, vagina, and other mucosal surfaces. By priming the
immune system with a standard vaccine and then pulling activated immune
system cells to the genital tract with cell-attracting chemicals, she's been
able to prevent development of herpes in mice. Iwasaki now is testing this
prime-and-pull vaccination strategy against HIV and exploring how harmless
viruses that live within the body affect the immune system.
Nicole King, Ph.D.
University of California, Berkeley
Nicole King fearlessly staked her postdoctoral research on a daring
hypothesis and a poorly understood organism. She set out to prove that
choanoflagellates, single-celled organisms that can also exist as
multicellular colonies, are the closest living relatives to animals and may
illuminate animal origins. While a possible relationship between
choanoflagellates and animals was first proposed in the 1840s,
choanoflagellates were ignored during the molecular era. King chose to
investigate animal origins using DNA sequencing and comparative genomics to
look for molecules and pathways that choanoflagellates share with
multicellular animals.
Her gamble paid off. Her research, continued in her laboratory at the
University of California, Berkeley, has revealed that choanoflagellates are
equipped with many genes required for animal multicellularity, including
molecules cells use to communicate with and adhere to one another—
indicating they evolved long before the origin of animals. King says the
single-celled ancestor of animals probably looked a lot like a
choanoflagellate.
Her most exciting recent finding came about when she solved a seemingly
mundane problem. Although some choanoflagellates readily form colonies in
the wild, they stubbornly refused to do so in the lab. The dilemma was
resolved when she discovered that prey bacteria from the natural environment
of the choanoflagellates produce a lipid that triggers colony development,
raising the possibility that a similar interaction may have contributed to
the evolution of animal multicellularity. Today, King is using the tools she
developed to investigate how single-celled choanoflagellates differentiate
and organize themselves into colonies. | p*****c
发帖数: 20445 | 3 Christopher D. Lima, Ph.D.
Memorial Sloan-Kettering Cancer Center
Christopher Lima doesn’t pick easy problems. A structural biologist, he is
investigating how cells attach small proteins—like ubiquitin and the
related molecule SUMO—to other proteins to modify their function or fate.
Alongside those studies, he is exploring the molecular mechanisms that
underlie RNA processing and degradation—modifications to an RNA copy of a
gene that influence its stability and ability to be used as a template for
protein production. These fundamental cellular processes present challenges,
because the cellular machines that carry them out are complex, often made
up of many proteins or parts. Further, they involve reactions in which many
of the structures Lima is trying to study exist only temporarily, changing
quickly as the reactions proceed.
Lima is known for using ingenious methods and sheer persistence to determine
the structures of the proteins and complexes involved in RNA processing and
protein modification and following up with genetic and biochemical
experiments that clarify how they function in cells. His work is revealing
how an RNA-degrading complex called the exosome recognizes damaged or
unneeded RNAs; how the small protein SUMO, which helps direct proteins to
certain parts of the cell and influences their interactions with other
molecules, gets attached to its targets; and how these processes are
regulated.
Harmit S. Malik, Ph.D.
HHMI Early Career Scientist
Fred Hutchinson Cancer Research Center
Tales of battles, ancient and modern, are written in our genes—and Harmit
Malik is their Homer. A geneticist, virologist, and evolutionary biologist,
Malik chronicles an endless genetic arms race not just between organisms and
pathogens but also within an individual species’ genome.
Malik sees the human genome as a tapestry documenting past evolutionary
conflicts. Delving deeper into genes that help fend off viral invaders,
Malik and his colleagues have shown that adaptations in those genes offer a
record of virus evolution. That insight created a whole new field, indirect
paleovirology, in which scientists try to identify ancient viruses by virtue
of the imprints they left on the evolution of host genes. The structure of
our genome reflects a “negotiated truce,” he says, and the best way to
understand that truce is to reconstruct the events that produced it. This
approach has profound implications for medicine as well as science, because
it uncovers new antiviral strategies, new mechanisms of immunity, and new
clues about autoimmune diseases like lupus.
Malik’s lab is also investigating evolutionary competition between
components that are involved in the essential process that ensures that
chromosomes divide and segregate equally during cell division. He has
pioneered the idea that chromosomal competition for evolutionary dominance
can drive the unexpectedly rapid evolution of these essential components.
These findings have direct implications for how chromosomal imbalances can
occur in cancer and for how two recently diverged species can become
reproductively isolated from each other.
Tirin Moore, Ph.D.
HHMI Early Career Scientist
Stanford University
Tirin Moore wants to understand how the brain’s sensory and motor networks
work together to produce higher cognitive functions. His studies of the
neural circuits and processes that control visual attention are advancing
scientists’ understanding of how the human brain extracts information from
the environment to guide behavior.
Moore identified the neural circuitry that enables us to focus our visual
attention on something of interest while ignoring irrelevant information in
the visual field. His research showed that neurons in the brain’s
prefrontal cortex that were previously known to control eye movement also
help focus attention, even in the absence of movements. When an animal plans
a gaze shift to a visual target, the prefrontal neurons fire more strongly.
This action modulates signals within the visual cortex, where visual
information is processed, which in turn enhances sensory signals related to
the target, and thus attention.
Moore believes that defects in this function are the root cause of attention
deficit hyperactivity disorder (ADHD) and that his research could lead to
improved treatments for this and other conditions that impair attention. For
example, people with ADHD have abnormal dopamine transmission in the
prefrontal cortex. He showed that altering dopamine levels within the
prefrontal cortex in the brains of macaque monkeys increased the fidelity of
sensory signals within the visual cortex, just as voluntarily directed
attention does.
Moore’s comprehensive studies of visual attention continue, and as he
develops new tools to address fundamental problems in systems-level
neurobiology, he intends to expand his research to other perceptual and
cognitive functions.
Vamsi K. Mootha, M.D.
Massachusetts General Hospital
Vamsi Mootha has a passion for mitochondria. These ancient cellular
organelles, which house the cell's power generators, can cause a host of
diseases when they malfunction. Mootha first learned of these conditions as
a medical student, and began both doing basic research on the organelle and
seeing his first patients with mitochondrial disease. These experiences led
him to dedicate his research training and professional lab to the biology of
this organelle.
Mootha aims to bridge the divide between molecular studies and the
physiology of complex systems. Mitochondria contain small amounts of their
own DNA, and Mootha was struck by how much research on mitochondrial
diseases focused its search there—even though most mitochondrial proteins
are actually encoded by DNA in the cell's nucleus. Using his background in
math and computational biology, he set out to create a more complete picture
of mitochondrial biology and its contribution to disease.
He has since resolutely pushed the field forward. On the physiology side,
his lab characterized the molecular identity of the mitochondria's calcium
uniporter, a key channel of communication between the organelle and its cell
. And on the disease side, he used cutting-edge and innovative approaches to
define the 1,100 proteins in mammalian mitochondria, developed
computational tools to predict protein function, and linked mitochondrial
gene mutations to human disease.
In less than a decade, Mootha's work in basic biology has led to genetic
diagnostics, prenatal screens, and a more complete understanding of an
organelle that can be involved in a multitude of common diseases, including
neurodegeneration, type 2 diabetes, and cancer. He sees hundreds of
mitochondrial components still waiting to be characterized, a multitude of
genetic and cellular pathways to describe, and the potential to find cures
for some devastating disorders.
Dyche Mullins, Ph.D.
University of California, San Francisco
Dyche Mullins says the most interesting questions in his lab often boil down
to this: How does a mindless mob of macromolecules actually become a living
cell? To achieve the sort of spatial organization associated with even the
simplest cells, tiny molecules must transmit and integrate information
across long distances—hundreds to hundreds of thousands of times their own
length.
One way to establish such long-range order is to assemble the individual
molecules into larger, ordered structures: membranes, cell walls, and
cytoskeletal polymers. The actin cytoskeleton, made up of actin filaments
and other molecules, is one such complex assembly. It enables cells to
change shape, to move, to transport cargo, and to establish polarity (making
one end of the cell different from the other). Scientists in the Mullins
laboratory focus on learning how cytoskeletal polymer networks are assembled
, how they function, and what roles they play in prokaryotic and eukaryotic
cells.
Mullins has discovered some of the key molecules and mechanisms that
choreograph assembly of the actin cytoskeleton. In particular, he showed
that a protein complex, called the Arp2/3 complex, creates branching
networks of filaments that push forward the leading edge of crawling cells.
His laboratory also identified mechanisms of actin assembly carried out by
proteins such as Spire and JMY, both of which are required for normal
embryonic development. In addition to identifying regulators and
understanding how they work, the Mullins laboratory is investigating how
cytoskeletal systems contribute to health problems such as drug-resistant
infections, metastatic cancers, and developmental defects.
Evgeny Nudler, Ph.D.
New York University
Taking risks and venturing into new areas of research have been common
threads in Evgeny Nudler’s career. He has made major discoveries in topics
as diverse as the mechanics of RNA synthesis, cellular adaptations to stress
, and bacterial resistance to antibiotics.
Nudler illuminated a fundamental principle of RNA synthesis, showing that
RNA polymerase works like a ratchet, powering forward and then backtracking
as it makes RNA. He then showed that this herky-jerky motion, which he
called “backtracking,” helps cells manage RNA growth and allows for gene
regulation and proofreading.
Nudler’s lab and another group discovered independently that messenger RNA
molecules called “riboswitches” sense cellular levels of metabolites—such
as vitamins, amino acids, ions, and other small molecules—and adjust gene
activity accordingly. Nudler’s group also identified an RNA molecule in
mammalian cells that, in combination with another factor, plays an important
role in sensing heat and other protein-damaging conditions.
Another discovery by Nudler’s team revealed a previously unknown defense
mechanism that bacteria use to fend off antibiotics. Humans use nitric oxide
and hydrogen sulfide to control physiological functions ranging from blood
pressure to neurotransmission. Nudler’s team has shown that bacteria
produce and use these gases for a different purpose—to protect themselves
from antibiotics, oxidative stress, and the immune system of their host.
Nudler next wants to learn how the bacteria that dwell harmlessly inside
other organisms, including humans, influence the aging of their hosts. To
tackle this question, he and his colleagues are now designing probiotic
strains of bacteria that significantly extend the lifespan of the roundworm
Caenorhabditis elegans.
Ardem Patapoutian, Ph.D.
Scripps Research Institute
Touch provides us with crucial information about our environment, yet it
remains poorly understood at the molecular level. Touch-sensitive cells can
warn of danger from hot, cold, and toxic substances. These cells can also
tell us when we experience a gentle touch or when a hammer accidentally hits
our finger. The sensing of mechanical forces and their translation into
chemical signals influence a variety of biological processes. Hearing
depends on mechanosenstion, and the sensory modality also controls the
function of the heart, blood vessels, lungs, and kidney.
Ardem Patapoutian has advanced the understanding of thermosensation with the
discovery of ion channels in touch-sensitive cells that respond to changes
in temperature. He calls them the body's molecular thermometers. For example
, one of them preferentially responds to cool temperatures and the cooling
compound menthol. Another, which also responds to cold, is a general sensor
of noxious chemicals, including ingredients in garlic and wasabi. Its
activation causes pain and inflammation.
How cells sense mechanical forces, like pressure and stretching, is one of
the last big unsolved questions in vertebrate sensory research, Patapoutian
says. It has proven difficult to pinpoint the molecules underlying cells'
sensitivity to mechanical forces, but here Patapoutian has broken new ground
, identifying two novel ion channels, Piezo1 and Piezo2, that are
responsible for that sensitivity. These channels are present in a wide
variety of tissues, and Patapoutian plans to investigate how they function
to regulate various biological processes, as well as how they may contribute
to disease. At the same time, he will continue to search for other sensory
ion channels. | p*****c
发帖数: 20445 | 4 Michael Rape, Ph.D.
University of California, Berkeley
Michael Rape’s love of science began in the basement of his parent’s house
, where he used to conduct rudimentary biochemistry experiments. Today, he
uses far more sophisticated methods to understand a complex process critical
to nearly all organisms: ubiquitylation. The term describes the attachment
of a regulatory protein called ubiquitin—named for its ubiquity—onto other
proteins. Ubiquitin tags communicate a wealth of information to the cell
about what a protein’s fate should be. Rape’s work has uncovered many
details about how ubiquitin gets attached to its target proteins and helped
elucidate the crucial roles ubiquitin tags play in cell division and cell
fate.
In human cells, getting ubiquitin on and off the right proteins at the right
times involves hundreds of enzymes acting on thousands of targets. When the
labeling system goes awry, diseases like cancer and Parkinson’s can result
. The loss of activity of one such ubiquitin-attaching enzyme is enough to
cause breast and ovarian cancers, for example. If scientists can figure out
how to manipulate ubiquitylation, they might be able to develop therapies
for many of these diseases. Rape developed a screening method to identify
enzymes involved in ubiquitylation and in the removal of ubiquitin. He plans
to use his setup to identify targets for potential drugs that activate or
inhibit these enzymes.
Peter W. Reddien, Ph.D.
HHMI Early Career Scientist
Massachusetts Institute of Technology
Scientists working to solve the mysteries of regeneration often look to
starfish or salamanders to gain insight, but Peter Reddien is committed to a
less photogenic organism: the humble planarian. These tiny flatworms have
amazing regenerative powers. Just a sliver of tissue can give rise to a
whole new worm. Reddien's work is revealing the secrets of planarians’
success.
Reddien's group found that planarians are equipped with stem cells with the
capacity to become any type of cell in the worm's body, and that these cells
give rise to new tissue during regeneration. Just one such cell is enough
to regenerate an entire worm. His lab has also discovered how wounded
planarians manage to regrow body parts in the right places. When a planarian
is wounded, a signaling pathway called Wnt instructs the regenerating cells
to grow a tail. When the worm needs a head, a gene called notum kicks in,
dampening the Wnt pathway. Silencing notum or genes in the Wnt pathway
generates worms with multiple heads or tails were generated.
Using the molecular tools he has developed for identifying genes controlling
regeneration, Reddien is continuing to investigate the sources of the worm'
s extraordinary regenerative powers. The insight he gains may lead to new
understanding of the genes and pathways that control tissue repair and stem
cell biology in humans. It will also help reveal what limits the human body'
s ability to regenerate lost or injured tissue.
Aviv Regev, Ph.D.
HHMI Early Career Scientist
Massachusetts Institute of Technology
Molecular networks are the information-processing devices of cells and
organisms, transforming extra- and intracellular signals into coherent
cellular responses. Aviv Regev uses computational and experimental
approaches to investigate how the molecular networks that regulate gene
activity rewire themselves in response to genetic and environmental changes
—in the short term and over millennia. She has developed techniques to
analyze how genes and regulatory networks in yeast have changed over the
course of 300 million years and how circuits change as immune cells respond
to pathogens or differentiate. Her algorithms are used in labs around the
world to analyze gene expression data and other information. Not content to
work solely in silico, her lab is also using cutting-edge experimental
techniques, such as inserting genes into cells with silicon nanowires, to
chart the molecular circuitry of T cells.
The computational wizardry of Regev and her colleagues has enabled them to
identify circuits and regulatory pathways that they can test and manipulate
at the lab bench. Data from the experiments in the lab can then be used to
improve the computational models. Working with dendritic cells (antigen-
presenting cells of the immune system), blood cells, and yeast, Regev has
identified dozens of regulators. Her group has confirmed some of these
molecular regulators by knocking out the corresponding genes in mice. She
and her colleagues are beginning to define which regulatory circuits have
changed and which have stayed the same over millions of years of evolution.
David Reich, Ph.D.
Harvard Medical School
Ever since modern humans evolved, groups of them have been on the move,
mixing with other groups they encountered. Geneticist David Reich is a world
expert at finding evidence of mixing between human populations. He has
shown that this mingling of genes is a profound part of human evolutionary
history.
His studies have also exposed some surprising dalliances in our species’
past. In 2010, Reich co-led a team that was the first to sequence and
analyze the genome of Neandertals. The data showed that the Neandertals
weren’t just our cousins—they were occasionally our mates, the source of
about 2 percent of the DNA in the genomes of present-day non-Africans. After
isolating DNA from a preserved finger bone, Reich and coworkers found that
a mysterious group called the Denisovans, who dwelled in Siberia around 50,
000 years ago, also left their genetic mark in the DNA of some present-day
people. His team has also applied its methods to medical questions. They
uncovered seven DNA alterations that might explain why prostate cancer is
about twice as common in African American men as in men of European ancestry.
This year, Reich and colleagues opened a state-of-the-art laboratory for
analyzing ancient DNA, which requires special precautions to prevent
contamination with modern DNA. He plans to use the facility to probe
European history and Native American history and to dig deeper into the
origins of India’s inhabitants, who are descended from people who lived in
northern India and a distinct group his team has identified from the
southern part of the country.
Russell E. Vance, Ph.D.
University of California, Berkeley
The human body is rife with microbes. They cover our skin, colonize our
digestive tracts, and coat our teeth. Not all cause harm. In fact, some of
these hitchhikers are helpful. To protect the body from disease, the immune
system must decide which invaders should be destroyed and which should be
ignored. But friendly microbes often look a lot like foes. How does the
immune system distinguish between the two?
Working at the interface of immunology and microbiology, Russell Vance has
discovered that the location of the microbe plays a key role in the immune
system's decision. Many pathogens access the interior of host cells to wreak
havoc, while harmless bacteria tend to be relegated to the spaces between
cells. To detect invaders, the immune system employs sensors called
inflammasomes. By confining these sensors inside cells, the immune system
avoids setting off false alarms.
Vance recently discovered that immune cells called macrophages contain an
inflammasome sensor that can detect flagellin, the protein that makes up the
whip-like appendages that many bacteria use to motor around. When this
sensor signals the presence of flagellin-containing invaders, the
macrophages self-destruct to prevent the infection from spreading. But that'
s not the whole story. In the coming years, Vance will continue to explore
the mechanisms that underlie the immune system's ability to destroy harmful
bacteria and disregard the harmless ones. Those mechanisms could be the key
to understanding why certain pathogens, like the bacterium that causes
tuberculosis, can be so deadly.
Johannes C. Walter, Ph.D.
Harvard Medical School
Johannes Walter studies how DNA genomes are copied, or replicated, before
cell division and how DNA damage is repaired to prevent errors in the
genetic blueprint. To this end, he employs a unique approach in which
purified DNA molecules are added to extracts of frog eggs, where they
undergo replication and repair outside the confines of a cell. Using this
highly tractable experimental system, Walter has uncovered how an enzyme
called the MCM2-7 helicase, which he's called the "first violin in the
symphony of DNA replication," separates the two strands of DNA in
preparation for genome duplication.
Another question he's addressed is how cells avoid making more than one copy
of their DNA. He showed that the process of genome duplication triggers the
destruction of a key initiator of DNA replication, thus preventing a second
round of replication. His team has also unraveled how cells repair a
hazardous form of DNA damage—called interstrand cross-links—that can block
replication by causing the two DNA strands to stick together. Walter and
his colleagues determined how this mechanism fails in Fanconi anemia, a
human genetic disease characterized by bone marrow failure and cancer
susceptibility. Walter's lab has recently turned its attention to
understanding how the proteins BRCA1 and BRCA2 repair DNA. Mutations in
BRCA1 and BRCA2 dramatically raise the risk of breast cancer.
Rachel I. Wilson, Ph.D.
HHMI Early Career Scientist
Harvard Medical School
After a few molecules waft into your nostrils, you know whether you’re
standing next to a fresh-baked apple pie or a pile of rotting apples. Rachel
Wilson aspires to learn how the brain translates sensory information such
as these aromas into impulses it can interpret and act on.
In the lab, Wilson and her team work to understand sensory processing using
fruit flies as their model organism. Her toolbox for studying fly perception
is well stocked. She devised a delicate technique for recording the
electrical activity of individual neurons in a fruit fly’s tiny brain,
which consists of about 100,000 neurons. Not only can she and her colleagues
eavesdrop on specific neurons, they can also pinpoint a neuron or group of
neurons, delete a cell from a neural circuit to gauge its function, and
tamper with genes to assay the roles of particular proteins.
Her team is now probing the function of a brain structure in fruit flies
called the antennal lobe, an olfactory relay station that is analogous to
the olfactory bulb in mammals. Wilson’s lab has discovered that the
antennal lobe reformats or “transforms” signals to allow the brain to
better extract information about odors in the environment. Some of the steps
in this transformation are similar to what occurs in the visual system,
suggesting that a core set of fundamental principles are shared by different
sensory systems. Wilson’s research group is continuing to branch out from
olfaction to study the rules of information processing in the auditory
system of fruit flies. This change in direction will permit Wilson to
compare and contrast which rules and algorithms are used by two very
different sensory systems.
Yukiko Yamashita, Ph.D.
University of Michigan
Stifled by conflicting expectations for women scientists in Japan, Yukiko
Yamashita found a welcoming home in the United States. As a postdoctoral
fellow at Stanford University, she learned “laid-back confidence,” she
recalls, and began a period of creative discovery that led her to the
University of Michigan, where she is now transforming the study of stem
cells.
A central question that has fascinated Yamashita is now her main research
focus: When stem cells divide, what determines which daughter cell will
remain a stem cell and which will differentiate into sperm or other tissue
types? Maintaining a balance between stem and differentiating cell
populations is critical because an excess of stem cells can lead to
tumorigenesis, whereas too many differentiated cells can deplete the stem
cell pool, reducing tissue regenerative capacity.
Examining cells in the fruit fly testis, Yamashita discovered the choice of
stem cell fate was regulated by cellular asymmetries. When a stem cell
divides, the daughter cell that retains the original “mother” copy of a
cell structure called the centrosome is the one that remains a stem cell.
Yamashita’s lab has also uncovered a key checkpoint in asymmetric stem cell
division–showing that the position of the centrosome determines whether
cell division will continue. Yamashita looks forward to designing and
carrying out experiments that are curiosity driven and that may yield new
examples of unappreciated asymmetries during stem cell division and
unexpected links between biological processes. | T****r
发帖数: 4006 | | i****g
发帖数: 3896 | | s*****g
发帖数: 7857 | 7 是
【在 i****g 的大作中提到】
: 只有何川一个华人？
| s******y
发帖数: 28562 | 8 恩，做nucleotide modification 的。
【在 i****g 的大作中提到】
: 只有何川一个华人？
| d********m
发帖数: 3662 | 9 河川的化学背景搞这个简直是绝配。做啥molecular biology的通通SB了吧 | s******y
发帖数: 28562 | 10 恩，感觉是经典分子生物问题用化学角度重新看。文章非常的impressive。
我在研究生院的时候曾经在rotation 的时候做过相关课题，当时我就感觉很烦的是很
多问题用分子生物的方法来做不清不楚，当时我还问那个时候的supervisor 说，为什
么没有人用物理或者化学方法来做这些问题？我都忘记她当时怎么回答我的了，呵呵。
另外，偷偷的说一下，才发现他其实还是我的校友，呵呵，下次碰到一定好好套个瓷。
【在 d********m 的大作中提到】
: 河川的化学背景搞这个简直是绝配。做啥molecular biology的通通SB了吧
| | | k*******n
发帖数: 21 | 11 我一直都觉得搞化学/物理的人来搞生物的，都是很大牌的教授。
【在 d********m 的大作中提到】
: 河川的化学背景搞这个简直是绝配。做啥molecular biology的通通SB了吧
| s*******7
发帖数: 399 | 12
===================
俺个人印象：科大的人团结，非常团结。
以前何川和金鹏有不少合作，一个学化学的，一个学生物的，俩人好像还同届，俩位科
大学子联手撞出不少paper，跨学科合作是王道啊！但何川真正的爆发是自转到RNA修饰
后，一发不可收拾，文章滚滚而来。
说起来俺和何川还有点那么一点点亲戚关系，不过俺知道他，他未必知道俺这颗草根，
哈哈。
俺10年前当何川刚刚拿到教职时就看好他是rising star，但没料到rising速度如此之
强之快。貌似何川还有个芝加哥大学从副教授升到正教授时间最短的记录，不到2年。
何川很低调，你看他们实验室照片就知道了，每次他都站在最不显眼的角落，以前拿他
们实验室集体照照片让人猜谁是老板，从来没有一个猜对的。人也实在，对华人很好，
很照顾中国学生，你陶瓷会有收获的。
【在 s******y 的大作中提到】
: 恩，感觉是经典分子生物问题用化学角度重新看。文章非常的impressive。
: 我在研究生院的时候曾经在rotation 的时候做过相关课题，当时我就感觉很烦的是很
: 多问题用分子生物的方法来做不清不楚，当时我还问那个时候的supervisor 说，为什
: 么没有人用物理或者化学方法来做这些问题？我都忘记她当时怎么回答我的了，呵呵。
: 另外，偷偷的说一下，才发现他其实还是我的校友，呵呵，下次碰到一定好好套个瓷。
| a***y
发帖数: 19743 | 13 中国人完败。
大多数是白人。还有犹太人。
两个日本人，两个印度人。一个中国人。
the
.
【在 p*****c 的大作中提到】
: A-D E-K L-P R-Z
:
:
:
:
: Peter Baumann, Ph.D.
: HHMI Early Career Scientist
: Stowers Institute for Medical Research
: Peter Baumann’s research focuses on beginnings and endings: beginnings in
: the form of reproduction in unisexual lizards and endings in the form of the
| b*******n
发帖数: 8420 | | c********r
发帖数: 1125 | 15 yamashita@ umich的当选完全不可理喻。。。。。
首先，她做得还可以，但是也就是还可以，重新炒作这个领域里的一些冷饭，发表的
review比研究文章多得多的人，呵呵。。。
做果蝇的，发育的，细胞／干细胞的比她强的老板甚至AP都一堆。。。她凭何德何能当
选HHMI?
以她的工作能当选HHMI early就要偷笑了。。。 |
|
