FARA Flash Talks
May is FA Awareness Month and one way to bring more awareness to FA is to share FARA funded research with the broader FA community and foster career development for young investigators.

With that in mind, FARA is proud to present: The FA Research Flash Talks series - featuring Young Investigators from FARA funded laboratories around the world. This four-part series will cover key aspects of FARA funded research from gene silencing and disease mechanisms to therapeutic avenues and clinical insights. Each session will include Flash Talks from four to five Young Investigators. Each Flash Talk will be limited to a maximum of five minutes and a single PowerPoint slide and will be suitable for a lay audience.  
 
The series starts tonight, Thursday, May 6th at 7pm (EDT), and will continue weekly. Click the button below to register for one, two, three, or all four of the sessions.
Pharma News
FARA launches the Industry Advisory Summit 

FARA has created a new forum through which industry partners developing therapeutics for FA can engage directly with FARA scientific leadership along with FA experts and thought leaders. This Industry Advisory Summit provides a forum where precompetitive initiatives and research being supported and led by FARA can be shared with industry leaders, in order to accelerate the progress in finding effective treatments for FA. As part of the FARA Industry Advisory Summit, industry leaders are invited to participate in quarterly round table type webinar meetings. The first meeting took place on April 20, 2021 and was attended by representatives of 16 pharmaceutical and biotech companies. The presentations centered around Potency Assay, Animal Models and Retrospective Cardiac Natural History Study. These were followed by breakout sessions to discuss new pre-competitive initiatives to identify knowledge gaps and need for preclinical tools, and clinical study design. Our next summit meeting will be scheduled for late June/early July. 

If you are interested in registering, please contact felicia.derosa@curefa.org. We look forward to working closely with our industry partners in 2021 to provide value and information in an up-to-the minute format. 
Healx launches partnership with Ataxia UK and FARA to find treatments for rare neurodegenerative condition 

Healx, the AI-powered, patient-inspired technology company accelerating the discovery and development of rare disease treatments at scale, is excited to announce its latest patient group partnerships. Working in collaboration with Ataxia UK and FARA, Healx will leverage its state-of-the-art AI platform and drug discovery expertise to develop novel treatments for Friedreich’s ataxia. At the heart of Healx’s technology is Healnet – their AI drug discovery platform. As one of the only AI companies in the world to focus specifically on rare diseases, Healx has developed the world’s most comprehensive biomedical knowledge graph for rare diseases which comprises millions of data points from clinical, pharmacological and scientific literature.  

Read the full press release here. 
FARA Funded Research, April 2021
Frataxin deficiency promotes endothelial senescence in pulmonary hypertension. 
Culley MK, Zhao J, Tai YY, Tang Y, Perk D, Negi V, Yu Q, Woodcock CC, Handen A, Speyer G, Kim S, Lai YC, Satoh T, Watson AM, Al Aaraj Y, Sembrat J, Rojas M, Goncharov D, Goncharova EA, Khan OF, Anderson DG, Dahlman JE, Gurkar AU, Lafyatis R, Fayyaz AU, Redfield MM, Gladwin MT, Rabinovitch M, Gu M, Bertero T, Chan SY. 

In this study, the authors hypothesize that frataxin (FXN) controls endothelial senescence, since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in pulmonary hypertension (PH). An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S-containing polymerases, promoting replication stress, DNA damage response, and senescence. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease. 
Other FA Research Publications, April 2021
Longitudinal structural brain changes in Friedreich ataxia depend on disease severity: the IMAGE-FRDA study. 
Selvadurai LP, Georgiou-Karistianis N, Shishegar R, Sheridan C, Egan GF, Delatycki MB, Harding IH, Corben LA. 
This study aimed to characterize longitudinal change in brain structure across cerebral and cerebellar grey and white matter using T1-weighted, diffusion-tensor, and magnetisation transfer magnetic resonance. Individuals with Friedreich ataxia had a greater rate of white matter volume loss than controls in the superior cerebellar peduncles and right peri-thalamic/posterior cerebral regions, and greater reduction in left primary motor cortex gyrification. Heterogeneity in Friedreich ataxia progression is observed at the neurobiological level, with evidence of earlier cerebellar and later cerebral degeneration. 


Remember Friedreich Ataxia even in a toddler with apparently isolated dilated (not hypertrophic!) cardiomyopathy: revisited. 
Baban A, Cicenia M, Travaglini L, Calí F, Vasco G, Francalanci P, Novelli A, Adorisio R, Amodeo A, Dallapiccola B, Bertini E, Drago F 
This study describes a toddler with apparently isolated severe heart failure, successfully managed with heart transplant (HT). The patient was diagnosed with FRDA at a postoperative stage due to minimal neurological manifestations. The study highlights the importance of taking in consideration this rare condition even in a toddler with apparently isolated cardiomyopathy and especially when conventional investigations give negative results. The authors discuss the potential trigger effect of heart transplant as a precipitating factor in manifesting neurological symptoms.


The Cardioprotective Mechanism of Phenylaminoethyl Selenides (PAESe) Against Doxorubicin-Induced Cardiotoxicity Involves Frataxin. 
Fu X, Eggert M, Yoo S, Patel N, Zhong J, Steinke I, Govindarajulu M, Turumtay EA, Mouli S, Panizzi P, Beyers R, Denney T, Arnold R, Amin RH. 
This study shows that phenylaminoethyl selenides (PAESe), an orally active selenium-based compound, attenuates doxorubicin (DOX)-mediated cardiac hypertrophy in athymic mice. Mechanistically, DOX impedes the stability of Frataxin (FXN), resulting in enhanced mitochondrial free iron accumulation and reduced aconitase activity. PAESe prevented the reduction of FXN levels and the ensuing elevation of mitochondrial free iron levels, possibly by enhancing glutathione activity and inhibiting ROS formation.  


Variable-Temperature Electrospray Ionization for Temperature-Dependent Folding/Refolding Reactions of Proteins and Ligand Binding. 
McCabe JW, Shirzadeh M, Walker TE, Lin CW, Jones BJ, Wysocki VH, Barondeau DP, Clemmer DE, Laganowsky A, Russell DH. 
This article describes a new variable-temperature electrospray ionization (vT-ESI) source that utilizes a thermoelectric chip to cool and heat the solution contained within the static ESI emitter. This design allows for solution temperatures to be varied from ∼5 to 98 °C with short equilibration times (<2 min) between precisely controlled temperature changes. The performance of the apparatus is demonstrated using ubiquitin and frataxin.  
The FARA Forum Webinars
The FARA Forum is a monthly webinar featuring investigators who have been awarded FARA grants. The webinar is open to FARA grant awardees, and it is held on the second Tuesday of every month. Upcoming Dates:


May 11, 2021 
5:00 PM ET Aseem Ansari, St. Jude Children’s Hospital  
5:45 PM ET Mirella Dottori, University of Wollongong, Australia  

June 8, 2021 
12:00 PM ET Tslil Ast, Mootha lab, Broad Institute 
12:45 PM ET Joshua Meisel, Mootha lab, Broad Institute 

July 13, 2021 
12:00:00 PM ET Javier Santos, Universidad de Buenos Aires 
12:45:00 PM ET Jaclyn Tamaroff, The Children's Hospital of Philadelphia 
FARA Newly Awarded Research Grants
General Research Grants

Mechanism of neuronal rescue by microglia expressing frataxin and characterization of neuronal defects in Friedreich’s ataxia.
Stephanie Cherqui – University of California, San Diego. 

Sphingolipid rheostat as a potential target for Friedreich’s Ataxia (FRDA).
Sara Anjomani-Virmouni – Brunel University. 
Meetings of Interest to the FA Community
24th American Society of Gene & Cell Therapy Annual Meeting,
May 11 – 14, 2021 – Virtual. Registration now open.

National Ataxia Foundation Ataxia Investigators Meeting (AIM),
May 24-27, 2021 – Virtual.

RNA Therapeutics Symposium, June 24-26, 2021 – Virtual.

Save the date for the inaugural International Congress for Ataxia Research (ICAR), March 15-18, 2022 - Orlando, Florida, USA.
Grant Opportunities
FARA research grants Kyle Bryant Translational Research Award and Bronya J. Keats International Research Collaboration Award - LOI deadline is May 15, General grants – next LOI deadline is July 1, 2021. See the 2021 FARA grant program priorities here.

FARA RFP: Pharmacodynamic Biomarker Development – This RFP promotes the discovery of technologies to measure frataxin or surrogates of frataxin in inaccessible tissues. The LOI submission deadline is July 01, 2021. Access the full RFP here.

FARA Award for Innovative Mindset - This Request For Proposal promotes the initial exploration of innovative, high-risk, high-gain, and potentially groundbreaking concepts in FA research. The proposed research project should include a well-formulated, testable hypothesis based on strong scientific rationale and study design. The presentation of preliminary and/or published data is encouraged, but not required. The Application Submission Deadline is June 1, 2021. Access the full RFP here.

CIRM - Various grant opportunities for stem cell-related projects in California.

Wellcome Trust Innovator Award (UK) - Funding focus: development of diagnostics and repurposed medicines for neurological disorders including rare diseases. No deadline. 
Job Advertisements
Three positions open in the Puccio Laboratory at the Institut Neuromyogène in Lyon (France) 
 
Defining the therapeutic window and threshold for neuronal gene therapy in Friedreich Ataxia: A 2-year funded engineer position
Our group focuses on hereditary cerebellar ataxias, rare neurodegenerative disorders that affect the cerebellum and/or the spinal cord. Our group is interested in unraveling the pathophysiological mechanisms implicated in cerebellar ataxias, with a particular focus on cerebellar ataxias linked to mitochondrial dysfunction. Furthermore, we aim at developing therapeutic approaches to cure these devastating diseases. We address these fundamental and medical questions by combining human genetics, mouse genetics, biochemistry, molecular and cell biology, pharmacology and AAV-based gene therapy. 

There are two objectives to this project, funded by the Friedreich Ataxia Research Alliance (FARA): to further develop gene therapy approaches for Friedreich ataxia and to explore the developmental component of the disease with a particular focus on the neuronal component of the disease. 
More information on the team can be found on the Puccio Lab Web site. 

Profile: 2-year position for an assistant engineer. Candidates must be highly motivated and have a M2 in biological science or neuroscience, or sufficient years of laboratory experience in the field. Hands-on experience with molecular techniques as well as animal work (Experimental animal certification level 1 or equivalent) is required. Prior experience with behavioral phenotyping, gene therapy, or neurodevelopment would be an asset. French speaking is NOT a requirement. Ability to work independently and within a team environment, computer literacy and good communication skills are required. 
 
AtaxiaXplorer, Common pathways underlying Purkinje neuron degeneration in Cerebellar Ataxias: A 3-year funded postdoctoral position:
Our group focuses on hereditary cerebellar ataxias, rare neurodegenerative disorders that affect the cerebellum and/or the spinal cord. Our group is interested in unraveling the pathophysiological mechanisms implicated in cerebellar ataxias, with a particular focus on cerebellar ataxias linked to mitochondrial dysfunction. Furthermore, we aim at developing therapeutic approaches to cure these devastating diseases. We address these fundamental and medical questions by combining human genetics, mouse genetics, biochemistry, molecular and cell biology, pharmacology and AAV-based gene therapy. 

Cerebellar ataxias represent a heterogeneous group of genetically inherited neurodegenerative diseases that is most often caused by Purkinje neuron dysfunction. Despite different genetic mutations causing cerebellar ataxia, the current research landscape points out toward substantial overlap of disease pathways. However, there is yet no comprehensive molecular analysis of degenerative mechanisms, and in particular in Purkinje neurons, that could prioritize molecular targets for therapeutic development. The overall objective of the research project is to identify common pathways underlying cerebellar cell-type vulnerability across cerebellar ataxias, with a major focus on Purkinje Neurons. The project is supported by the Fondation pour la Recherche Médicale (FRM). More information on the team can be found on the Puccio Lab Web site. 

Profile: 3-year position for 1 postdoctoral researcher. Candidates must be highly motivated and have a PhD in biological science or neuroscience. Hands-on experience with molecular and cellular biology techniques applied to mouse brain characterization is required. Prior experience with RNA sequencing (single cell or bulk), other -omics technologies and bioinformatics would be an asset. Experimental animal certification level 1 or equivalent would be an asset. French speaking is NOT a requirement. Ability to work independently and within a team environment, computer literacy and good communication skills are required. 
 
TREAT-ARCA, Designing a toolbox of paradigmatic treatments for a targeted molecular medicine approach to autosomal-recessive ataxias: A 3-year funded postdoctoral position:
Our group focuses on hereditary cerebellar ataxias, rare neurodegenerative disorders that affect the cerebellum and/or the spinal cord. Our group is interested in unraveling the pathophysiological mechanisms implicated in cerebellar ataxias, with a particular focus on cerebellar ataxias linked to mitochondrial dysfunction. Furthermore, we aim at developing therapeutic approaches to cure these devastating diseases. We address these fundamental and medical questions by combining human genetics, mouse genetics, biochemistry, molecular and cell biology, pharmacology and AAV-based gene therapy. 

The current project, funded by the European Joint Programme for Rare Diseases, aims at developing novel therapeutic approaches and at discovering and validating biomarkers that will enable to follow treatment for COQ8A ataxia, a rare recessive ataxia linked to CoQ10 metabolism. 
More information on the team can be found on the Puccio Lab Web site. 

Profile: 3-year position for a postdoctoral researcher. Candidates must be highly motivated and have a PhD in biological science or neuroscience. Experimental animal certification level 1 or equivalent is required. Hands-on experience with molecular and cellular biology techniques as well as animal work is required. Prior experience with gene therapy and/or pharmacology, RNA sequencing or bioinformatics would be an asset but is not required. French speaking is NOT a requirement. Ability to work independently and within a team environment, computer literacy and good communication skills are required. 
 
When/how to apply: Starting date September 2021, but due to the pandemic restrictions, we will accommodate the selected candidates. Deadline for submission is fixed to May 31st 2021. Please send your application in a single pdf (3 pages max), including your CV, summary of your previous research experiences, and contact information of 2-3 references to: helene.puccio@inserm.fr 
 
About the Puccio lab: The Puccio group is provided with a fully equipped molecular and biochemistry laboratory, and is embedded in a highly collaborative and multidisciplinary environment at the Institut NeuroMyoGène, in the highly dynamic and international city of Lyon, France. The candidate will benefit from an excellent work environment, including various state-of–the art research facilities in the Lyon-Est campus. Lyon is considered as one of the most attractive metropoles in Europe, with a strong signature in biological science, architecture, & gastronomy 
Post-doctoral fellow position - Napierala Laboratory, University of Alabama at Birmingham

A post-doctoral fellow position is immediately available to study mechanisms of Friedreich’s ataxia in the Napierala Laboratory, within the Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham. We are seeking a highly motivated scientist to join our multi-disciplinary group who is interested in investigating how chromatin changes are implicated in the pathogenesis of repeat expansion diseases.

The position requires experience utilizing mammalian cell culture models, and proficiency working with induced pluripotent stem cells is desirable. Preference will be given to candidates demonstrating expertise in chromatin biology, transcriptional regulation and post-translational histone modifications, including experience performing ChIP, ChIP-seq and RNAseq experiments.

The postdoctoral fellow duties will include but are not limited to: organizing and implementing complex research plans (independently and as part of a team), developing new methods, collecting and recording data, and analyzing and critically interpreting data. The successful candidate will be expected to possess excellent communication skills and present their research findings regularly to peers within the Department and at national and international meetings. The postdoctoral fellow will also participate in preparation of grant applications and publications.

We offer competitive pay at or above NIH recommended level and relocation assistance.

To be considered for this position, please email your CV and cover letter to mnapiera@uab.edu.
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