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Mei Zeng Receives Genome Customization Award

March 29, 2011 By

Mei Zeng, a postdoc in Nelson Lau’s lab (Biology) has been selected to receive a postdoctoral fellowship award – the Genome Customization Award (TGCA) from Cellectis Bioresearch. The TGCA award was established by Cellectis Bioresearch in 2010 with the goal of spreading the use of meganucleases for genome customization throughout the life sciences

Meganucleases are endodeoxyribonucleases characterized by a large recognition site (12 to 40 base pairs) — so large that it  generally only occurs once in any given genome. The Lau group will apply the custom meganucleases to improve transgenesis of Xenopus tropicalis for RNA interference methodologies. The most widely used transgenesis method utilizes the yeast meganucleases I-SceI which cuts both the transgene vector and an unknown site in the genome into which the transgene gets integrated. This method has several limitations: it requires a large number of embryos for injection and screening,  the integration sites cut by I-Sce-I are unknown and likely stochastic, and it ultimately produces only 5-10% of germline transmission. The custom meganucleases engineered by Cellectis Bioresearch target a known single site (24bp) within the genome, allowing for increased specificity and efficiency of transgene intergration. Mei and colleagues hope to use the rational design to enforce the systemic constitutive expression of a short hairpin RNA cassette in a vertebrate model.

Marc Le Bozec, CEO of Cellectis Bioresearch, presented the award to Drs. Nelson Lau and Mei Zeng on March 16, 2011 at the grand opening of Cellectis Bioresearch Inc facilities in Cambridge, Massachusetts.

Filed Under: awards, Biology, labs, postdocs Tagged With: , , , , ,

Older Adults are Better at Spotting Fake Smiles

March 16, 2011 By

Studies of aging and the ability to recognize others’ emotional states tend to show that older adults are worse than younger adults at recognizing facial expressions of emotion, a pattern that parallels findings on non-social types of perception. Most of the previous research focused on the recognition of negative emotions such as anger and fear. In a study “Recognition of Posed and Spontaneous Dynamic Smiles in Young and Older Adults” recently published in Psychology and Aging, Derek Isaacowitz’s Emotion Laboratory set out to investigate possible aging effects in recognizing positive emotions; specifically, the ability to discriminate between posed or “fake” smiles and genuine smiles. They video-recorded different types of smiles (posed and genuine) from younger adults (mean age = 22) and older adults (mean age = 70). Then we showed those smiles to participants who judged whether the smiles were posed or genuine.

Across two studies, older adults were actually better at discriminating between posed and genuine smiles compared to younger adults. This is one of the only findings in the social perception literature suggesting an age difference favoring older individuals. One plausible reason why older adults may be better at distinguishing posed and spontaneous smiles is due to their greater experience in making these nuanced social judgments across the life span; this may then be a case where life experience can offset the effects of negative age-related change in cognition and perception.

This was the first known study to present younger and older adult videotaped smiles to both younger and older adult participants; using dynamic stimuli provides a more ecologically valid method of assessing social perception than using static pictures of faces. The findings are exciting because they suggest that while older adults may lose some ability to recognize the negative emotions of others, their ability to discriminate posed and genuine positive emotions may remain intact, or even improve.

The Emotion Laboratory is located in the Volen Center at Brandeis. First author Dr. Nora Murphy (now Assistant Professor of Psychology at Loyola Marymount University) conducted the research as a postdoctoral research fellow, under the supervision of Dr. Isaacowitz, and second author Jonathan Lehrfeld (Brandeis class of 2008) completed his Psychology senior honors thesis as part of the project. The research was funded by the National Institute of Aging.

Filed Under: labs, postdocs, Psychology, Undergrads Tagged With: , , , , ,

What are best friends for? Insights from 10 million friendships

February 19, 2011 By

Why do people have best friends? Why do we think of some individuals as “better” friends than other individuals? Why rank friends at all? And what is so special about the apex of the ranking, our “best” friend?

Peter DeScioli, a Kay Fellow at Brandeis University, and colleagues recently shed light on these questions by collecting a dataset of over 10 million people’s friendship decisions from the MySpace social network. The results support the “alliance hypothesis” which is based on the idea that people depend on their friends in conflicts. The findings were recently published in the journal Perspectives on Psychological Science.

MySpace has a feature that allows users to rank their “Top Friends,” providing a unique data source for testing how well different variables explain people’s rankings of friends. The alliance hypothesis predicts that people will feel closest to friends who rank them higher than others. Here’s why: If you need your friend to take your side in an argument, then they will have to side against someone else—which is unlikely if they are better friends with your adversary. The fewer people ranked above you, the more you can rely on your friend to take your side. According to the theory, people unconsciously track this strategic information and it shapes how we feel about our friends.

It turns out that the importance of friend rank was highly significant. Comparing first- and second-ranked friends, 69% chose for first-rank the individual who ranked them better. This was a considerably larger effect than the next best predictor, geographic proximity. The effects of sex, age, and popularity were small by comparison. Moreover, friend rank increased in strength when the analysis was extended to first- versus third- through eighth-ranked friends. In short, we now have 10 million more reasons to wonder if human friendship might be more strategic than it seems.

Other comment:

http://www.physorg.com/news/2011-02-friendships-built-alliances.html

http://www.epjournal.net/blog/2011/02/who-is-your-best-friend%E2%80%99s-best-friend/

Filed Under: postdocs, Psychology Tagged With: , , ,

Can a “chemical rope” help treat ALS?

November 22, 2010 By

In this week’s issue of PNAS, Brandeis postdoc Jared Auclair and Chemistry grad student Kristin Boggio, together with Professors Greg Petsko, Dagmar Ringe, and Jeffrey Agar discuss Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized in the most common form of familial amyotrophic lateral sclerosis. Working from the hypothesis that the mechanism of the toxicity involves dimer destabilization and dissociation as an early step in SOD1 aggregation, they looked for mechanisms to stabilize SOD1 using chemical cross-linking. Cross-linking the dimer using 2 adjacent cysteine residues results in substantial stabilization of relevant SOD1 mutants.

A "Chemical rope" stabilizes SOD1 protein. Mutations that destabilize SOD1 in motor neurons are associated with familial ALS

Read more about Prof. Agar, this research, and its potential for this technique in the treatment of ALS at Brandeis NOW

Filed Under: Biochemistry, chemistry, grad students, labs, postdocs Tagged With: , , , , , ,

Visually driven intrinsic plasticity

November 19, 2010 By

In mammals including humans, proper development of the cortex is heavily dependent on sensory experience. Neurons in sensory cortex are subject to a “use it or lose it” rule, whereby if they are deprived of sensory input during a critical period of development, they lose the ability to respond altogether. This loss of responsiveness could occur through synaptic changes (synaptic plasticity), or through changes in the intrinsic ability of neurons to fire action potentials (intrinsic plasticity).

Up until now experience-dependent development has largely been ascribed to  synaptic plasticity mechanisms.  In the cover article in this week’s issue of Neuron, (Nataraj et al., Neuron 68, 750–762, November 18, 2010), Brandeis postdocs Kiran Nataraj, Nicolas Le Roux, Marc Nahmani and Sandrine Lefort from the lab of Professor Gina Turrigiano show that a form of intrinsic plasticity termed “long-term potentiation of intrinsic excitability”, or LTP-IE, plays an important role in experience-dependent refinements of cortical circuits. This study shows that sensory drive normally keeps cortical output neurons active by triggering LTP-IE, and sensory deprivation reduces the ability of these neurons to fire by preventing the activation of this form of plasticity. This suggests that LTP-IE serves a “use it or lose it” function in cortical output neurons, gating cortical output by keeping active neurons responsive, while suppressing the output of  inactive neurons.

Filed Under: Biology, labs, Neuroscience, postdocs Tagged With: , , , ,

For ClC transporters, breaking up is hard to do

November 15, 2010 By

Many ion channels and transporters exist as oligomers with each subunit containing a distinct transport pathway.  A classic example is the ClC family of chloride channels and transporters that are homodimeric with a pathway for chloride permeation or chloride/proton anti-port through each subunit.  Because of their dimer structure, they have come to be known as “double-barreled shotguns” for chloride movement across the membrane.

Since each subunit appears to possess the complete machinery required for transport, it is  often wondered whether ClCs need to be dimeric in order to carry out function.  In a study published last week in Nature, Brandeis researchers Janice Robertson, Ludmila Kolmakova-Partensky and Professor Christopher Miller answer this question.  By introducing two tryptophan mutations at the dimer interface, they designed a variant of a ClC transporter that could be purified and crystallized as an isolated monomer.  With this, they were able to determine that the monomer alone was fully capable of carrying out chloride and proton transport function.  These results show that the dimer is not required and that the monomer is the fundamental unit of transport in ClCs.  The question of why ClCs evolved as dimers remains a key question for understanding membrane protein structure.

Filed Under: Biochemistry, labs, postdocs Tagged With: , , , , , ,

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