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Neurodevelopmental Disorders: Mechanisms and Therapeutics
A Keystone Symposium connecting genetics, functional genomics, developmental neurobiology, and industry to identify convergent mechanisms and therapeutic opportunities in neurodevelopmental disorders.
Repurposing CRISPR to turn genes on and off
UC Berkeley Molecular & Cell Biology seminar (Divisions of Biochemistry, Biophysics & Structural Biology; Cell Biology, Development & Physiology; and Genetics, Genomics, Evolution & Development) by Luke Gilbert of UCSF on repurposing CRISPR systems to activate and silence genes.
Massively Parallel Studies of Enhancer Function
UC Berkeley Molecular & Cell Biology seminar (Division of Genetics, Genomics & Development) by Barak Cohen of Washington University in Saint Louis on massively parallel experimental studies of enhancer function.
Research Associate (Fixed Term)
We seek a highly motivated Postdoctoral Research Associate to join the laboratory of Professor Kathy Niakan. We are based in the Loke Centre for Trophoblast Research (LCTR), in the Department of Physiology, Development and Neuroscience. A successful candidate will help to develop pioneering research projects to provide fundamental insights into human biology and inform novel strategies for stem cell biology and post-implantation development of human embryos. The aims of research projects in the lab are to characterise early lineage specification in human pre- and early post-implantation embryos. We seek to explore a range of methods to establish robust and reproducible cutting-edge single cell molecular analysis, imaging, functional genomics techniques and stem cell models to understand early lineage specification mechanisms in human embryos. Our laboratory aims to utilise the knowledge gained from these studies to provide fundamental insights into human biology. We also aim to use this knowledge to facilitate the development of robust and reproducible implantation models, novel human stem cells and stem cell-based models of human development. We perform comparative analysis of human embryogenesis to several other mammalian species, pluripotent stem cells and integrated stem cell models of human embryos. The successful candidate will be energetic, focused, and productive with a desire to work in a congenial, dynamic, and collaborative research environment. Excellent organizational, analytical, and communication skills are essential. Candidates should hold a PhD in a relevant subject. Please refer to the person specification for a full list of essential skills and qualifications. The University actively supports equality, diversity and inclusion and encourages applications from all sections of society. The Department of Physiology, Development & Neuroscience particularly encourages women and candidates from a Black, Asian or Minority Ethnic background to apply for this vacancy. We will support visa application if assistance is needed. We have a legal responsibility to ensure that you have the right to work in the UK before you can start working for us. Any job application you submit to us will be assessed using criteria based on the knowledge, skills and experience required for the relevant post. You will not be treated less favourably than another applicant on the grounds of national origin. However, any offer of employment we make to you will be conditional upon you gaining permission to work in the UK. For further information: http://www.jobs.cam.ac.uk/right/have/ To find out more about the lab visit our website at: https://niakanlab.com/ To find out more about the LCTR please visit our website at: https://www.trophoblast.cam.ac.uk/ Fixed-term: The funds for this post are available for 3 years in the first instance. Once an offer of employment has been accepted, the successful candidate will be required to undergo a basic disclosure (criminal records check) check and a security check. Click the 'Apply' button below to register an account with our recruitment system (if you have not already) and apply online. To apply for this post, please submit a CV and a motivation letter detailing why you want to be part of this project and how this post will be a good stepping-stone for your career. We also need the contact details for two people who can provide a professional reference. Closing date: midnight on 13th September 2026. Please quote reference PM50266 on your application and in any correspondence about this vacancy. The University actively supports equality, diversity and inclusion and encourages applications from all sections of society. The University has a responsibility to ensure that all employees are eligible to live and work in the UK.
Microglial efferocytosis: Diving into the Alzheimer's Disease gene pool
Genome-wide association studies and functional genomics studies have linked specific cell types, genes, and pathways to Alzheimer’s disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, and thus the activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) in the etiology of AD. These genes converge on pathways (endocytosis/phagocytosis, cholesterol metabolism, and immune response) with critical roles in core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting relevant genes identified in the latest AD genetics and genomics studies, and describe how they may contribute to AD pathogenesis. Investigating the functional impact of AD-associated variants and genes in microglia is essential for elucidating disease risk mechanisms and developing effective therapeutic approaches." https://doi.org/10.1016/j.neuron.2022.10.015
Towards a More Authentic Vision of the (multi)Coding Potential of RNA
Ten of thousands of open reading frames (ORFs) are hidden within transcripts. They have eluded annotations because they are either small or within unsuspected locations. These are named alternative ORFs (altORFs) or small ORFs and have recently been highlighted by innovative proteogenomic approaches, such as our OpenProt resource, revealing their existence and implications in biological functions. Due to the absence of altORFs from annotations, pathogenic mutations within these are being ignored. I will discuss our latest progress on the re-analysis of large-scale proteomics datasets to improve our knowledge of proteomic diversity, and the functional characterization of a second protein coded by the FUS gene. Finally, I will explain the need to map the coding potential of the transcriptome using artificial intelligence rather than with conventional annotations that do not capture the full translational activity of ribosomes.
CRISPR-based functional genomics in iPSC-based models of brain disease
Human genes associated with brain-related diseases are being discovered at an accelerating pace. A major challenge is an identification of the mechanisms through which these genes act, and of potential therapeutic strategies. To elucidate such mechanisms in human cells, we established a CRISPR-based platform for genetic screening in human iPSC-derived neurons, astrocytes and microglia. Our approach relies on CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa), in which a catalytically dead version of the bacterial Cas9 protein recruits transcriptional repressors or activators, respectively, to endogenous genes to control their expression, as directed by a small guide RNA (sgRNA). Complex libraries of sgRNAs enable us to conduct genome-wide or focused loss-of-function and gain-of-function screens. Such screens uncover molecular players for phenotypes based on survival, stress resistance, fluorescent phenotypes, high-content imaging and single-cell RNA-Seq. To uncover disease mechanisms and therapeutic targets, we are conducting genetic modifier screens for disease-relevant cellular phenotypes in patient-derived neurons and glia with familial mutations and isogenic controls. In a genome-wide screen, we have uncovered genes that modulate the formation of disease-associated aggregates of tau in neurons with a tauopathy-linked mutation (MAPT V337M). CRISPRi/a can also be used to model and functionally evaluate disease-associated changes in gene expression, such as those caused by eQTLs, haploinsufficiency, or disease states of brain cells. We will discuss an application to Alzheimer’s Disease-associated genes in microglia.