ASCB Rainbow


Philadelphia, USA • December 2

2017 ASCB Doorstep Meeting: Register Now! Limited to 200 Attendees!

Abstract Deadline: Oct. 11

Separate registration & fee required
(Only available to ASCB members. Not a member? Join here)
Please contact Heather Smith with any questions.

Doorstep Meeting OverviewScheduleSpeaker DetailsRegistrationCancellation PolicyHousing/TravelSupport Options

Meeting Overview

This doorstep symposium features leaders in the cell biology of brain development, function, and degeneration, including investigators whose studies of protein folding and intracellular trafficking have yielded insights into neurodegenerative diseases as well as investigators whose studies of brain development and brain disease have uncovered a central role for critical cell biological processes.

The meeting will provide a clear overview of the field, with significant time allotted for discussion and interaction between audience and speakers, with the goal of inspiring the ACSB community to tackle the cell biology of the brain.  Frank Bradke, German Center for Neurodegenerative Diseases (DZNE e.V.) and Kelsey C. Martin, UCLA David Geffen School of Medicine are the meeting organizers.

Students and postdocs who would like to explore opportunities in brain research are encouraged to apply. There will be an opportunity for you to submit an abstract during the registration process.  Those selected to present will present during one of two hour-long poster sessions, held during the morning and afternoon breaks.  The deadline to submit an abstract is Wednesday, October 11.  Submitting an abstract does not guarantee it will be accepted.   Abstracts submitted for the 2017 ASCB | EMBO Meeting will not be considered!

Registration also includes admission to the 2017 ASCB | EMBO Meeting Fred Kavli Keynote Lecture with Cori Bargmann, of The Rockefeller University and Chan Zuckerberg Initiative, and the welcome reception to follow.

Doorstep Meeting Schedule

8:00 am Registration Begins
8:00 am Breakfast
8:35 – 8:45 am Welcome
8:45 – 9:15 am Paola Arlotta
Harvard University
9:15 – 9:45 am Carla Shatz
Stanford Bio-X, Stanford University
9:45 – 10:15 am Don Cleveland
Ludwig Institute, Universitry of California at San Diego
10:15 – 11:15 am AM Poster Session
11:15 – 11:45 am Susan Ackerman
University of California, San Diego
11:45 am – 12:15 pm J. Paul Taylor
St. Jude Children’s Research Hospital/HHMI
12:15 – 2:15 pm Lunch w/Roundtable Discussions
2:15 – 2:45 pm Erika Holzbaur
University of Pennsylvania Perelman School of Medicine
2:45 – 3:15 pm F. Ulrich Hartl
Max Planck Institute of Biochemistry
3:15 – 4:15 pm PM Poster Session
4:15 – 4:45 pm Thomas L. Schwarz
Boston Children’s Hospital and Harvard Medical School
4:45 – 5:15 pm Dennis Selkoe
Harvard Medical School/Brigham & Women’s Hospital
5:15 – 5:25 pm Wrap – Up
6:00 pm Cori Bargmann
The Rockefeller University and Chan Zuckerberg Initiative
2017 ASCB | EMBO Meeting Fred Kavli Keynote Lecture
(keynote admission included with Doorstep Meeting registration)

*subject to change

Speaker Details

Development and Reprogramming of Neuronal Diversity in the Neocortex

Paola Arlotta, Harvard University

The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of several neuron subtype-specific and pan-neuronal genes. I will describe our recent work on the governing principles underlying developmental generation and postnatal maintenance of excitatory pyramidal neuron diversity in the cerebral cortex. I will also discuss how pyramidal neuron diversity impacts the behavior of other cell types during cortical development and discuss the critical effect on oligodendrocytes to guarantee generation of normal patterns of myelin distribution in different cortical layers. Once development is complete, it is well known that pyramidal neurons become permanently postmitotic and do not change their class-specific identity for the life span of the organism. I will show that during a defined window of postmitotic development (“critical window of nuclear plasticity”) pyramidal neurons can still change their class-specific identity in vivo and in turn reprogram the wiring of the afferent inhibitory circuit.

 

Saving the Synapse: MHC Class I and Synapse Pruning during Development and in Alzheimer’s Disease

Carla Shatz, Stanford Bio-X, Stanford University

Synaptic connections in adult brain are highly precise, but they do not start out that way. Precision emerges as connections are pruned or strengthened during a developmental process requiring neural activity. Activity also regulates neuronal gene expression. In an in vivo unbiased screen, Major Histocompatibility Class I (MHCI) genes were found to be regulated by activity, expressed in neurons, and located at synapses (Corriveau et al, 1998; Huh et al, 2000). To assess requirements for MHCI in CNS, mutant mice lacking specific MHCI genes Kb and Db, were studied. Synapse pruning in the developing visual system fails, and ocular dominance (OD) plasticity in visual cortex is greater than in WT (Lee et al, 2014; Datwani et al, 2009). In a search for receptors for neuronal MHCI, PirB was found expressed in subsets of neurons throughout mouse CNS. In PirB KO mice, OD plasticity is enhanced (Syken et al., 2006), LTP and LTD are altered, and the pruning of dendritic spines on cortical pyramidal neurons is deficient not only during development in PirB KO mice (Djurisic et al, 2013; Vidal et al, 2016), but also when a soluble decoy receptor is infused in adult WT mice: Acute blockade of PirB in adult WT cortex triggers formation of new spines and functional synapses, and also restores visual function to an amblyopic eye (Bochner et al, 2014). Thus PirB, like MHCI, appears to regulate synapse pruning and to “brake” synaptic plasticity throughout life. The commonality of phenotypes in these mutant mice suggests a model in which PirB may bind and transduce signals from MHCI ligands in neurons. Moreover, without PirB, mice do not succumb to the devastating effects of Beta Amyloid- a main culprit for synapse and memory loss in Alzheimer’s disease (Kim et al, 2013). Together, results imply that these molecules, thought previously to function only in immunity, also act at neuronal synapses to regulate synapse pruning and plasticity in response to new experience. Changes in their function could contribute to developmental disorders such as Schizophrenia, and Alzheimer’s disease.

Supported by NIH Grants EY02858, MH071666, Mathers Charitable Foundation and Ruth K. Broad Biomedical Research Foundation

 

Gene Silencing Therapy for Neurodegenerative Disease

Don Cleveland, Ludwig Institute, University of California at San Diego

Exciting discoveries in the genetics of human neurodegenerative disease have fueled multiple efforts for – at last – development of “on mechanism” therapeutics in the major neurodegenerative diseases. Currently, there is no disease modifying therapies now for any of the major diseases. I will cover how the combination of efforts using gene silencing with designer DNA drugs, adenoviral associated gene vectors, and genome editing mediated by site specific nucleases now raises the possibility of development of effective disease-modifying therapies.

 

Dysfunction of Protein Translation in Neurodegeneration

Susan Ackerman, University of California, San Diego/HHMI

Neurodegenerative disorders affect many people, particularly in the aging population, yet the cause of these disorders is largely unknown. Using a forward genetic approach in mice, our lab has identified several novel molecular mechanisms that underlie CNS development and neuron death. Importantly, this phenotype-driven approach allows the identification, without a priori assumptions, of molecules critical to these processes. Furthermore, we use forward genetics to identify genes that modify the expressivity of the phenotype caused by the primary mutation. Together these approaches have identified new mechanisms of neurodegeneration and have demonstrated that dysfunction of protein translation greatly impacts neuronal homeostasis in the aging mammalian brain.

 

  Dynamic RNA-protein Assemblies in Neurological Disease

  J. Paul Taylor, St. Jude Children’s Research Hospital/HHMI

Eukaryotic cells partition their contents into numerous specialized structures (organelles) that create microenvironments to facilitate specific functions. Membrane-less organelles such as RNA granules differ from classical membrane-delimited compartments in that they behave like liquid droplets that rapidly assemble and disassemble in response to changes in the cellular environment. Membrane-less organelles include nucleoli, Cajal bodies, speckles, paraspeckles, and PML bodies in the nucleus, as well as P bodies, stress granules, and RNA transport granules in the cytoplasm. Paradigm-shifting advances over the past year have revealed that diverse membrane-less organelles assemble via liquid-liquid phase separation (LLPS) of low sequence complexity domains that are particularly enriched in RNA-binding proteins (RBPs) such as TDP-43, hnRNPA1, hnRNPA2B1, TIA-1 and FUS. Importantly, mutations in these RBPs are causative of degenerative diseases, such as amyotrophic lateral sclerosis, frontotemporal dementia and inclusion body myopathy. We have hypothesized that underlying basis of these diseases is disturbance of phase transitions that alters the dynamic properties of membrane-less organelles. I will present evidence that the mutations in disease-associated proteins alter the biophysical and material properties of these proteins in liquid assemblies and result in perturbed dynamics and/or functions of multiple membrane-less organelles.

 

Autophagy Dynamics in Neuronal Homeostasis and Neurodegeneration

Erika Holzbaur, University of Pennsylvania Perelman School of Medicine

Neurons are highly polarized cells that are post-mitotic and must survive for decades in humans.  These cells rely on homeostatic mechanisms to maintain cellular health, including autophagy and mitophagy.  Deficits in autophagic flux lead to the accumulation of protein aggregates and dysfunctional mitochondria, and are characteristic of neurodegenerative diseases such as Parkinson’s, Huntington’s, and ALS.  Live cell imaging of autophagy in neurons has revealed a dynamic pathway that is altered in both aging and disease.

 

Chaperone Functions in Protein Quality Control and Implications in Neurodegenerative Disease

F. Ulrich Hartl, Max Planck Institute of Biochemistry

The past two decades have witnessed a paradigm shift in our understanding of cellular protein folding. While the three-dimensional structures of functional proteins are determined by their amino acid sequences, we now know that in the crowded environment of cells newly-synthesized polypeptides depend on molecular chaperone proteins to reach their folded states efficiently and at a biologically relevant time scale. Assistance of protein folding is provided by different types of chaperone which act to prevent misfolding and aggregation, often in an ATP-dependent mechanism. Once folded, many proteins continue to require chaperone surveillance to retain their functional states, especially under conditions of cell stress. Failure of the chaperone machinery to maintain proteostasis, i.e. the conformational integrity and balance of the cellular proteome, facilitates the manifestation of diseases in which proteins misfold and form toxic aggregates. These disorders include Parkinson’s, Huntington’s and Alzheimer’s disease.

I will discuss recent findings from model systems suggesting that toxic protein aggregation in neurodegenerative disease is both a symptom and a cause of proteostasis decline.

 

Neuronal Mitostasis and Parkinson’s Disease

Thomas L. Schwarz, Boston Children’s Hospital and Harvard Medical School

Neurons last a lifetime, but proteins do not; proteins require constant turnover and synthesis.  For mitochondrial proteins this is particularly true, because the reactive oxygen species formed by the electron transport chain are prone to damaging mitochondrial proteins. This presentation will review what we know about the synthesis and degradation of mitochondria in the special context of neuronal architecture and the problems posed by having mitochondria up to a meter away from the nuclear DNA encoding their proteins. Particular attention will be given to the evidence that Parkinson’s can be a mitochondrial disorder and to the role of PINK1 as a trigger of the mitophagic clearance of damaged mitochondria.  PINK1 poses a particular problem for neurons because its normal halflife is just minutes; PINK1 mRNA transport on mitochondria and local translation can solve the problem of allowing a short-lived protein to support mitophagy throughout the axonal and dendritic arbors.

 

The Cell Biology of Protein Misfolding in Alzheimer’s and Parkinson’s Diseases

Dennis Selkoe, Harvard Medical School/Brigham & Women’s Hospital

Misfolding and progressive aggregation of specific proteins appears to be etiologic in several human neurodegenerative diseases. Many studies have examined the process of protein misfolding in vitro, resulting in valuable insights, but to what extent findings in pure in vitro mixtures reflect the situation in intact biological systems is unclear. Our laboratory has focused for over three decades on living neurons, animal models, and human brain tissue to learn more about the in vivo characteristics and bioactivities of endogenous forms of amyloid β-protein (Aβ), tau protein and α-synculein (αSyn) in human neurodegeneration. Here, I will describe recent work on the effects of natural oligomers of Aβ isolated from Alzheimer’s disease cortex on iPSC-derived human neurons, including potent protection by certain monoclonal antibodies. I will then discuss our discovery that α-synuclein occurs physiologically in α-helical tetramers in intact neurons and that these rapidly disassemble upon cell lysis, yielding the ‘natively unfolded’ monomers that have long been the focus of α-synuclein research. We have generated mice expressing “tetramer-abrogating” α-synuclein mutations; they develop nigrostriatal and cortical lesions, decreased tyrosine hydroxylase, and a progressive motor phenotype that includes tremor and gait defects which respond in part to L-DOPA administration. This recent work has implications for the initiation of Parkinson’s disease and other human synucleinopathies and suggests their potential prevention by compounds that stabilize physiological α-synuclein tetramers.

Registration

Click Here or the blue button above to Register for the Doorstep Meeting >>>

Separate Registration & Fee Required for the 2017 ASCB | EMBO Meeting.

You must be an ASCB member to attend the 2017 ASCB Doorstep Meeting.  Not a member?  Join Now.

If you attend both the 2017 ASCB | EMBO Meeting and the 2017 ASCB Doorstep Meeting, the Doorstep Meeting cost is discounted 30%*.  The discount only applies to fully paid registrants of the 2017 ASCB | EMBO Meeting.

Member Rates*

Registration

(If registered for the 2017 ASCB | EMBO Meeting*)

Registration

(If NOT registered for the 2017 ASCB | EMBO Meeting)

ASCB Regular Member $175 $250
ASCB Postdoctoral Member $154 $220
ASCB Graduate Student Member $126 $180
ASCB Undergraduate Student Member $126 $180

*Please Note: In order to get the discount you have to either:

  1. Already be registered for the 2017 ASCB | EMBO Meeting
  2. Register for the 2017 ASCB | EMBO Meeting and the 2017 ASCB Doorstep Meeting at the same time

If you register for the 2017 ASCB Doorstep Meeting, then go back and register for the 2017 ASCB | EMBO Meeting you will NOT get the discount.

See Cancellation to learn about the cancellation policy.

Cancellation Policy

Meeting registration is nontransferable. Meeting registration is nonrefundable after November 17, 2017. The organizers will honor requests for refunds if they are in writing and are received by the ASCB no later than November 17. Please note that cancellations are subject to a processing fee of $20 for students and $40 for all others. No refunds will be issued for requests received after November 17. Please send a request for cancellation to hsmith@ascb.org.

Please Note: Registration refunds will not be issued after November 17 for denied.

Housing & Travel

The 2017 ASCB Doorstep Meeting: Cell Biology of Degeneration and Repair in the Nervous System is being held in conjunction with the 2017 ASCB | EMBO Meeting in Philadelphia, Pennsylvania. The links below will lead you to the Housing and Travel pages on the 2017 ASCB | EMBO Meeting site.

ASCB encourages you to take advantage of the great rates secured for the 2017 ASCB | EMBO Meeting in Philadelphia and book within the ASCB room block.

Click on the designated link below for more information on the following:

Support Opportunities

Cell Biology of Degeneration and Repair in the Nervous System
ASCB Doorstep Meeting
Held in conjunction with 2017 ASCB/EMBO Meeting
Philadelphia, PA, December 2, 2017

The Cell Biology of Degeneration and Repair in the Nervous System ASCB Doorstep Meeting will be held on Saturday, December 2, 2017—the first day of the ASCB/EMBO Meeting, in Philadelphia, PA.

This doorstep symposium features leaders in the cell biology of brain development, function, and degeneration, including investigators whose studies of protein folding and intracellular trafficking have yielded insights into neurodegenerative diseases as well as investigators whose studies of brain development and brain disease have uncovered a central role for critical cell biological processes.

The meeting will provide a clear overview of the field, with significant time allotted for discussion and interaction between audience and speakers, with the goal of inspiring the ACSB community to tackle the cell biology of the brain.

Organized by Kelsey Martin, UCLA, and Frank Bradke, DZNE, the small meeting will facilitate networking and discussion. Other confirmed speakers include Erika L. F. Holzbaur, University of Pennsylvania Perelman School of Medicine; F. Ulrich Hartl, Max Planck Institute of Biochemistry; Carla J. Shatz, Stanford Bio-X James H. Clark Center; J. Paul Taylor, St. Jude Children’s Research Hospital; Dennis J. Selkoe, Brigham & Women’s Hospital; Susan Ackerman, University of California, San Diego; Paola Arlotta, Harvard University; Don W. Cleveland, Ludwig Institute for Cancer Research; and Peter Walter, UCSF.

This is a great opportunity to engage with this focused community. Make sure your company is visible by supporting the Doorstep Meeting with one of the following options:

 Gold 25K  Silver 15K  Bronze 5K
Acknowledgment by the meeting chair from the dais and on signage throughout the meeting.
Complimentary registrations for the Doorstep Meeting 3 2 1
Complimentary mailing list of Doorstep Meeting attendees (postal addresses only)  
Opportunity to place literature on table in the meeting room (200 pieces max)    
Acknowledgment in Doorstep Meeting Program and website, on signage at the 2017 ASCB/EMBO Meeting, and in the ASCB Newsletter
Gold Support – $25,000
  1. Acknowledgment by the meeting chair from the dais
  2. Supporter’s name on signage at the meeting and by registration
  3. Three complimentary registrations for the Doorstep Meeting
  4. Complimentary mailing list for Doorstep Meeting attendees (postal addresses only)
  5. Opportunity to place Literature on table in the meeting room (100 pieces max)
  6. Acknowledgment in Doorstep Meeting Program and website, on signage at the 2017 ASCB/EMBO Meeting, and in the ASCB Newsletter
Silver Support – $15,000
  1. Acknowledgment by the meeting chair from the dais
  2. Supporter’s name on signage at the meeting and by registration
  3. Two complimentary registrations for the Doorstep Meeting
  4. Complimentary mailing list for Doorstep Meeting attendees (postal addresses only)
  5. Acknowledgment in Doorstep Meeting Program and website, on signage at the 2017 ASCB/EMBO Meeting, and in the ASCB Newsletter
Bronze Support – $5,000
  1. Acknowledgment by the meeting chair from the dais
  2. Supporter’s name on signage at the meeting and by registration
  3. One complimentary registration for the Doorstep Meeting
  4. Acknowledgment in Doorstep Meeting Program and website, on signage at the 2017 ASCB/EMBO Meeting, and in the ASCB Newsletter

If you would like to support the Doorstep Meeting in a different manner than listed above, please contact SPARGO, Inc., Exhibit, Sponsorship and Advertising Sales and Management, or call 1-703-631-6200 or 1-800-564-4220. We are always interested in your suggestions!

 

Special Thanks To: