Over the past few years, we have been working on an internationally collaborative project to identify a human induced pluripotent stem cell (iPSC) line that performs well across the board to underpin large-scale collaborative studies. Together we found one cell line, KOLF2.1J, that performs well across the board after we deeply analyzed its genetic background and stability, and its ability to be efficiently gene edited by CRISPR/Cas9 and differentiated into many different functional cell types. The cell line and its derivatives are now available with minimal restrictions and cost to the research community via a user-friendly website from the Jackson Laboratories (JAX). The substantial team effort was initiated by Michael Ward and Mark Cookson at the NIH who co-lead the iPSC neurodegenerative disease (INDI) consortium and Bill Skarnes at JAX whose team has developed highly efficient protocols for gene editing. A multitude of groups around the world generously contributed data to further characterise the performance of KOLF2.1J, and the project was made possible by the tireless efforts of Caroline Pantazis, Andrian Yang, Erika Lara, Justin McDonough, Cornelis Blauwendraat, Liong Peng, John Marioni, and many others. The KOLF2.1J cell line and its applications are beautifully described in accessible language developed with the help of the Chan Zuckerberg Initiative’s Neurodegeneration Challenge Network who generously helping support these efforts that have the potential to broadly impact the stem cell and neuroscience fields.
News
Welcome to Simone and Tian!
We’re delighted that Simone Mazzaferro and Tian Tian have started in the lab! Simone is an experienced electrophysiologist who trained at Oxford Brookes and the Mayo Clinic, and will be studying neuronal responses to nutrients, hormones, and drugs relevant to metabolic disease. Tian has experience in developmental biology, electrophysiology, and optical recording of action potentials and is keen to broaden her skills to improve neuronal maturation and pursue forward programming to hypothalamic cell types of interest.
Black Lives Matter
Our group’s values of equity and respect are more important than ever to affirm and broadcast in light of the ongoing and largely peaceful protests associated with the Black Lives Matter (BLM) movement. Racism and discrimination are unfortunately pervasive, and also affect academia. We stand with BLM in the peaceful struggle for justice and equality. Part of the problem is the spread of divisive language and misinformation on social media, and we’re proud to support an open letter to Mark Zuckerberg calling for action on posts that might endanger people’s lives or well-being.
Florian T. Merkle named New York Stem Cell Foundation – Robertson Investigator
Florian was named as one of 6 Robertson Investigators from the New York Stem Cell Foundation. This early career award of $1,500,000 will support the Merkle laboratory’s efforts to mechanistically connect obesity-associated phenotypes to cellular and organismic phenotypes, and to screen for potential anti-obesity drugs in vitro and test their effects in vivo.
P53 paper published in Nature
We found that approximately 5% of human pluripotent stem cell lines carry inactivating mutations in the master tumor suppressor TP53 (p53). This work is now published online in the journal Nature. The mutations we observed are frequently seen in cancer, and also lead to increased growth or survival in cultured stem cells. Since human stem cell lines are being therapeutically transplanted into humans, these findings provide an opportunity to identify and discard potentially dangerous cell preparations. This work was initiated in the laboratories of Kevin Eggan and Steve McCarroll at Harvard University and the Broad Institute, and completed after the establishment of the Merkle Lab.
Welcome to Dr. Daniela Razolli and Dr. Ying Xue
The Merkle lab is honoured to host Ying Xue, a MD/PhD who is visiting Cambridge for 1 year. Although she has only been here a short time she has already done a lot to CRISPR/Cas9-based gene editing pipelines up and running in the lab.
We are also excited to welcome Daniela, who is visiting Cambridge for 6 months from the lab of Licio Velloso in Brazil. Daniela will be examining the effects of free fatty acids (FFA) on the physiology of human hypothalamic neurons.
Welcome, Ying and Daniela!
Welcome to Dr. Julie Jerber
The Merkle lab welcomes Julie Jerber, who will work as a joint postdoc with Dan Gaffney (WT-Sanger Institute) and Oli Stegle (EMBO-EBI) to analyse the contributions of common genetic variants to neurodegenerative disease. Julie joins us from Rockefeller University. Welcome!
Florian awarded the CJ Herrick award in neuroanatomy
Florian was honoured to receive the Charles Judson Herrick award in Neuroanatomy at the American Association of Anatomists conference (Chicago, Illinois, USA, 2017): http://www.anatomy.org/annual-meeting-2017.html
Previous awardees have included Mark Tessier-Lavigne, Cori Bargmann, Mahendra Rao, and Feng Zhang.
Florian to present CamBioScience keynote 21/11
Florian will give the Keynote presentation at the upcoming CamBioScience intensive course on Genome Editing on Monday, November 21 at 6PM GDT.
Florian to deliver whole exome sequencing webinar 22/11
Florian and Kevin Eggan will present a webinar sponsored by StemCell Technologies on Tuesday, November 22 at 11AM EST entitled “Whole Exome Sequencing Reveals Selective Pressures and Dominant Negative Mutations in hPSC Cultures”.
Frances defends M.Phil successfully
Congratulations to Frances St. George-Hyslop, who successfully defended her M.Phil. project from the Farooqi and Merkle laboratories. Frances is now pursuing her Ph.D. in brain evolution at the University of Cambridge. We wish her all the best.
Bas Brouwers receives EMBO Fellowship
Bas Brouwers received an EMBO Fellowship for his project to study obesity-associated mutations in the serotonin 2C receptor, to be performed with Prof. Sadaf Farooqi and in the Merkle Lab.
Julia Becker receives Erasmus Scholarship
Julia Becker’s work to characterise heterogeneity among POMC neurons with Giles Yeo and in the Merkle lab has been supported by an Erasmus Scholarship.