JBS Offers “Bio-Inspired Design” Course

Maria de Boef Miara, Lecturer in Biology at Brandeis University, will be leading a course titled Bio-Inspired Design this summer (June 1 thru August 7, 2015). Bio-Inspired Design is part of the Justice Brandeis Semester (JBS). JBS combines courses and experiential learning to provide complete, immersive experiences so students can deeply examine a specific area of study.

Bio-Inspired Design is designed for students from a wide spectrum of disciplines, but may be particularly appealing to students in Biology, Biological Physics, Environmental Studies or HSSP areas. This is a 10-week course providing 12 credits.

Students in Bio-Inspired Design will spend the summer working with biologists, engineers and artists in a variety of settings. They will explore intriguing life forms and develop the quantitative tools needed to work at the intersection of form and function.

Division of Science Summer Undergraduate Research Fellowships (2015)

The Division of Science wishes to announce that, in 2015, we will again offer Division of Science Summer Undergraduate Research Fellowships for Brandeis students doing undergraduate research.  These fellowships are funded by generous alumni and corporate donations.

The due date for applications  is February 17, 2015,  at 6:00 PM EST.

Division of Science Summer Undergraduate Research Fellowships will provide $5000 in stipend support to allow students to do summer research (housing support is not included). Students who will be rising Brandeis sophomores, juniors, or seniors in Summer 2015 (classes of ’16, ’17, and ’18), who in addition are working in a lab in the Division of Science at the time of application, are eligible to apply. A commitment from a Brandeis faculty member to serve as your mentor in Summer 2015 is required.

The Division of Science Summer Program will run from May 26 – July 31, 2015. Recipients are expected to be available to do full time laboratory research during that period, and must commit to presenting a poster at the final poster session on July 30, 2015.

The application form is online (Brandeis login required). Questions that are not answered in the online FAQ may be addressed to Steven Karel <divsci at brandeis.edu>.

How does the brain decide whether you like what you eat?

When we encounter a taste, we appreciate both its chemosensory properties and its palatability—the degree to which the taste is pleasurable or aversive. Recent work suggests that the processing of this complex taste experience may involve coordination between multiple brain areas. Dissecting these interactions help understand the organization and working of the taste system.

F4.largeThe lateral hypothalamus (LH) is a region of the brain important for feeding. In a rodent, damage the LH, and the rodent may starve itself to death; stimulate it, and you get a curious mix of voracious eating and expressions of disgust over what is being eaten. Such data suggest that LH plays a complex game of balancing escape and avoidance, palatability and aversion, during the evaluation of a taste stimulus. Little is known, however, about how neurons in LH actually respond to tastes of different valences.

Brandeis postdocs Jennifer Li and Takashi Yoshida. undergraduate Kevin Monk ’13, and Associate Professor of Psychology Don Katz have recently published a study of neuronal reponses in LH in the Journal of Neuroscience. They have shown that taste-responsive neurons in LH break neatly down into two groups–one that responds preferentially to palatable tastes and one to aversive tastes. Virtually every taste neuron in LH could be identified as a palatable- or aversive-preferring neuron. In addition, even without considering the specific tastes to which a particular neuron responded, these two groups of neurons could be differentiated according to their baseline firing rate, shape of response, and tuning width. While these neurons were spatially intermingled, several pieces of data (functional connectivity analysis, relationship to responses in amygdala and cortex) suggest that they are parts of distinct neural circuits. These results offer insights into the multiple feeding-related processes that LH manages, and how the hypothalamus’ role in these processes might be related to its connection to other parts of the taste system.

Li JX, Yoshida T, Monk KJ, Katz DB. Lateral Hypothalamus Contains Two Types of Palatability-Related Taste Responses with Distinct Dynamics. J Neurosci. 2013;33(22):9462-73.

Summer undergraduate research fellowships for 2013

The Division of Science wishes to announce that, in 2013, we will again offer up to ten Division of Science Summer Undergraduate Research Fellowships for Brandeis students doing undergraduate research.  These fellowships are funded by generous alumni donations.

The due date for applications is February 15, 2013

Division of Science Summer Undergraduate Research Fellowships will provide $5000 in stipend support to allow students to do summer research (housing support is not included). Students who will be rising Brandeis sophomores, juniors, or seniors in Summer 2013 (classes of ’14, ’15, and ’16), who in addition are working in a lab in the Division of Science at the time of application, are eligible to apply. A commitment from a Brandeis faculty member to serve as your mentor in Summer 2013 is required.

The Division of Science Summer Program will run from May 29 – Aug 2, 2013. Recipients are expected to be available to do full time laboratory research during that period, and must commit to presenting a poster at the final poster session on Aug 1, 2013.

The application form is online (Brandeis login required). Questions may be addressed to Steven Karel <karel@brandeis.edu>.

Other programs available in 2013 will include the two NSF-funded REU programs sponsored by the MRSEC and the Program in Cell and Molecular Visualization. The REU programs are primarily aimed at students visiting for the summer from other institutions. There are also Traineeships for Undergraduates in Computational Neuroscience through a grant from the National Institute on Drug Abuse. The computational neuroscience traineeships run through the summer and continue into the academic year.

What a failed drug does (and is there hope for latrepirdine?)

Latrepirdine (Dimebon) was initially used as an antihistamine drug in Russia. It was later found to be neuroprotective, and entered phase II clinical trials in the US for both Alzheimer’s disease and Huntington’s disease. However, Dimebon failed in a US-based phase II replication trial of a prior successful Russian phase II trial of mild-to-moderate AD. Given the initial promise of the drug and split results,  as well as the lack of treatments for neurodegenerative diseases, there in is significant interest in understanding the underlying molecular mechanism(s) for the drug’s effects.

In a paper appearing this week in Molecular Psychiatry, Brandeis researchers in the Petsko-Ringe lab, including postdoc Shulin Ju and undergraduate Jessica Liken ’11, used yeast models of neurodegenerative disease associated proteins to show that Dimebon specifically protects yeast from the cytotoxiciy of α-synuclein, a protein involved in Parkinson’s disease. They further showed that protection is mediated through its up-regulation of autophagy pathway. In collaboration with Sam Gandy‘s group at Mount Sinai School of Medicine, these findings were further confirmed and validated in neuronal cell and animal models.

Given these observations, disparities in the contribution of α-synuclein to the neuropathology between the Russian and US Dimebon studies might also explain, at least in part, the inconsistency of the cognitive benefit in the two trials. If this speculation is correct, then it may be interesting to test for benefits of Dimebon in treating synucleinopathies such as Parkinson’s disease, Lewy body dementia, REM sleep disorder and/or multiple system atrophy.

see also: press release from Mt. Sinai Alzheimer’s Diesease Research Center

Steele JW (*), Ju S(*), Lachenmayer ML(*), Liken J, Stock A, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Protter AA, Martins RN, Ehrlich ME, Yue Z, Petsko GA, Gandy S. Latrepirdine stimulates autophagy and reduces accumulation of alpha-synuclein in cells and in mouse brain. Molecular psychiatry. 2012.

Steele JW(*), Lachenmayer ML(*), Ju S, Stock A, Liken J, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Fraser P, Westaway D, St George-Hyslop PH, Szabo P, Relkin NR, Buxbaum JD, Glabe CG, Protter AA, Martins RN, Ehrlich ME, Petsko GA, Yue Z, Gandy S. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer’s mouse model. Molecular psychiatry. 2012.

Dynamics of double-strand break repair


In a new paper in the journal Genetics, former Brandeis postdoc Eric Coïc and undergrads Taehyun Ryu and Sue Yen Tay from Professor of Biology Jim Haber’s lab, along with grad student Joshua Martin and Professor of Physics Jané Kondev, tackle the problem of understanding the dynamics of homologous recombination after double strand breaks in yeast. According to Haber,

The accurate repair of chromosome breaks is an essential process that prevents cells from undergoing gross chromosomal rearrangements that are the hallmark of most cancer cells.  We know a lot about how such breaks are repaired.  The ends of the break are resected and provide a platform for the assembly of many copies of the key recombination protein, Rad51.  Somehow the Rad51 filament is then able to facilitate a search of the entire DNA of the nucleus to locate identical or nearly identical (homologous) sequences so that the broken end can pair up with this template and initiate local copying of this segment to patch up the chromosome break.  How this search takes place remains poorly understood.

The switching of budding yeast mating type genes has been a valuable model system in which to study the molecular events of broken chromosome repair, in real time.  It is possible to induce synchronously a site-specific double-strand break (DSB) on one chromosome, within the mating-type (MAT) locus.  At opposite ends of the same chromosome are two competing donor sequences with which the broken ends of the MAT sequence can pair up and copy new mating-type sequences into the MAT locus.

Normally one of these donors is used 9 times more often than the other.  We asked if this preference was irrevocable or if the bias could be changed by making the “wrong” donor more attractive – in this case by adding more sequences to that donor so that it shared more and more homology with the broken ends at MAT.  We found that the competition could indeed be changed and that adding more homologous sequences to the poorly-used donor increased its use.


In collaboration with Jané Kondev’s lab we devised both a “toy” model and a more rigorous thermodynamic model to explain these results.  They suggest that the Rad51 filament carrying the broken end of the MAT locus collides on average 4 times before with the preferred donor region before it actually succeeds in carrying out the next steps in the process that lead to repair and MAT switching.

Dynamics of homology searching during gene conversion in Saccharomyces cerevisiae revealed by donor competition Eric Coïc , Joshua Martin, Taehyun Ryu, Sue Yen Tay, Jané Kondev and James E. Haber. Genetics. 2011 Sep 27 2011 Sep 27

Cryo-electron tomography and the structure of doublet microtubules

In a new paper in PNAS entitled “Cryo-electron tomography reveals conserved features of doublet microtubules“, Assistant Professor of Biology Daniela Nicastro and coworkers describe in striking new detail the structure and organization of the doublet microtubules (DMTs), the most conserved feature of eukaryotic cilia and flagella.

Cilia and flagella are thin, hair-like appendages on the surface of most animal and lower plant cells, which use these organelles to move, and to sense the environment. Defects in cilia and flagella are known to cause disease and developmental disorders, including polycystic kidney disease, respiratory disease, and neurological disorders. An essential feature of these organelles is the presence of nine outer DMTs (hollow protein tubes) that form the cylindrical core of the structure known as the axoneme. The doublet microtubule is formed by tubulin protofilaments and other structural proteins, which provide a scaffold for the attachment of dynein motors (that drive ciliary and flagellar motility) and regulatory components in a highly specific and ordered manner.

To address long-standing questions and controversies about the assembly, stability, and detailed structure of DMTs , the Nicastro lab used a high-resolution imaging technique, cryo-electron microscope tomography (cryo-ET), to probe the structure of DMTs from Chlamydomonas (single-celled algae) and sea urchin sperm flagella. Cryo-ET involves:

  1. rapid freezing of the sample to cryo-immobilize the molecules without forming ice crystals,
  2. tilting the specimen in the electron microscope to collect ~70 different views from +65° to –65°,
  3. computational alignment of the views to calculate a tomogram (a three-dimensional reconstruction of the imaged sample), and
  4. computational averaging of repeating structures in the tomogram to reduce noise and increase resolution.

Cryo-ET provided the necessary resolution to show that the B-tubules of DMTs are composed of 10 protofilaments, not 11, and that the inner and outer junctions between the A- and B-tubules are fundamentally different (see figure). The outer junction, crucial for the initial formation of the DMT, appears to be formed by interactions between the tubulin subunits of three protofilaments with unusual tubulin interfaces, but one of these protofilaments does not fit with the conventionally accepted orientation for tubulin protofilaments. This outer junction is important physiologically, as shown by mutations affecting the usual pattern of posttranslational modifications of tubulin. In contrast, the inner junction is not formed by direct interactions between tubulin protofilaments. Instead, a ladder-like structure that is clearly thinner than tubulin connects protofilaments of the A- and B-tubules.

The level of detail also allowed the Nicastro lab to show that the recently discovered microtubule inner proteins (MIPs) located within the A- and B-tubules are more complex than previously thought. MIPs 1 and 2 are both composed of alternating small and large subunits recurring every 16 and/or 48 nm along the inner A-tubule wall. MIP 3 forms small protein arches connecting the two B-tubule protofilaments closest to the inner junction, but does not form the inner junction itself. MIP 4 is associated with the inner surface of the A-tubule along the partition protofilaments, i.e., the five protofilaments of the A-tubule bounded by the two junctions with the B-tubule.

The Nicastro lab plans to build on this foundation in future work on the molecular assembly and stability of the doublet microtubule and axoneme, and hope to use it to elucidate molecular mechanisms of ciliary and flagellar motility and signal transduction in normal and disease states.

Other authors on the paper include Brandeis postdocs Xiaofeng Fu and Thomas Heuser, Brandeis undergrad Alan Tso (’10), and collaborators Mary Porter and Richard Linck from the University of Minnesota.

Beckman Scholarships and URP Awards for Summer 2011

Beckman Scholars and Undergraduate Research Program Winners

Summer 2011

Beckman Scholars

The 2011 Beckman Scholars are:

Frank Scangarello (mentor: Suzanne Paradis, Biology)
Multivalent Metalloproteases Inhibitors to Increase Small Molecule Avidity and Selectivity to Study Semaphorin4D-Cleavage Mediated Synaptic Nerve Development

Zhequan Xu (mentor: Christine Thomas, Chemistry)
Novel Catalyst Design for Green Fuels

URP Recipients

(only students from the Division of Science are included in this list)

Heather Bernstein ’12 (Language & Linguistics; Neuroscience) with Prof. Stephen Van Hooser
Stimulus Therapy & its Implications for Rehabilitation: Using Channelrhodopsin-2 to determine spike time-dependent plasticity in neurons of the primary visual cortex in postnatal ferrets at eye opening

James En Wai Chin ’14 (Chemistry) with Prof. Lizbeth Hedstrom
IMP dehydrogenase nucleic acid association (How do IMPDH mutants affect IMPDH nucleic acid binding?)

Nimrod Deiss-Yehiely ’12 (Biology) with Prof. Sacha Nelson
A mouse model for Infantile Spasms involving TTX

Scott Finkelstein ’12 (Biology) with Prof. Paul Miller
Comparative Success of Strategies in a Continuous Iterated Prisoner’s Dilemma

Jessica Friedman ’13 (Biochemistry) with Prof. Tom Pochapsky
Insights into Substrate Recognition in Cytochrome P450cam

Julie Miller ’12 (Neuroscience) with Prof. Stephen Van Hooser
Roles of Inhibitory Neurons in Cortical Development

Anna Slavina ’12 (Psychology) with Prof. Art Wingfield
Selective syntactical attention among bilingual speakers

Sophie Travis ’13 (Biochemistry) with Prof. Dagmar Ringe
In vitro characterization of VPS35

Akash Vadalia ’12 (Biology; HSSP) with Prof. Angela Gutchess
Cross-Cultural Differences in the Specificity of Memory for Objects and Contexts

Alison White ’13 (Psychology) with Prof. Art Wingfield
Monitoring the Capacity of Short Term Memory

Abigail Zadina ’13 (Psychology) with Prof. Michael Rosbash
Huntington’s Disease: Insights into Mechanisms Involving Circadian Systems

Detecting Mutations the Easy Way

Recent Brandeis Ph.D graduate, Tracey Seier (Molecular and Cell Biology Program), Professor Sue Lovett, Research Assistant Vincent Sutera, together with former Brandeis undergraduates Noor Toha, Dana Padgett and Gal Zilberberg have developed a set of bacterial strains that can be used as “mutational reporters”.  Students in the Fall 2009 BIOL155a, Project Laboratory in Genetics and Genomics, course also assisted in the development of this resource. This work has recently been published in the journal Genetics.

These Escherichia coli strains carry mutations in the lacZ (β-galactosidase) gene that regain the ability to metabolize lactose by one, and only one, specific type of mutation. This set allows environmental compounds to be screened for effects on a broad set of potential mutations, establishing mutagen status and the mutational specificity in one easy step.

This strain set is improved over previous ones in the inclusion of reporters that are specific for certain types of mutations associated with mutational hotspots in gene. Mutations at these sites occur much more frequently than average and involve DNA strand misalignments at repeated DNA sequences rather than DNA polymerase errors. Such mutations are associated with human diseases, including cancer progression, and have been under-investigated because of the lack of specific assays. Using this strain set, Seier et al. also identified a mutagen, hydroxyurea, used in the treatment of leukemia and sickle cell disease, which affects only the “hotspot” class of mutations. This strain set, which will be deposited in the E. coli Genetic Stock Center,  will facilitate the screening of potential mutagens, environmental conditions or genetic loci for effects on a wide spectrum of mutational events.

 

 

Left: E. coli colonies showing lacZ mutant revertants (blue pimples) arising on a white colony on growth medium containing the beta-galactosidase indicator dye,  X-gal

 

Older Adults are Better at Spotting Fake Smiles

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.

Protected by Akismet
Blog with WordPress

Welcome Guest | Login (Brandeis Members Only)