The Integrative Neurophysiology (INF) division at the Center for Neurogenomics and Cognitive Research (CNCR) at VU offers a fully funded 4-year PhD project. The focus of the project is on elucidating molecular mechanisms of fast neuronal signaling. A critical requirement of fast neuronal computation and cognitive function is the ability of neurons to generate and maintain fast and stable output - action potentials. Because of difficult access to living human neurons, their function in supporting cognition remains largely unexplored. Our lab has extensive experience in studying the function of human neurons from neurosurgery patients. We recently showed that fast electrical signaling in human neurons directly links to cognitive ability in the same individuals (refs 1,2 below). In the current project, we aim to elucidate molecular mechanisms that underlie fast electrical signaling by manipulating expression of specific genes in human neurons, in organotypic slice cultures as well as human iPSC-derived neurons using CRISPRa/CRISPRi (3,4). We will target genes that have been associated with cognitive ability in human subjects (5). Thereby, we aim to reveal what molecular mechanisms enable human neurons to achieve fast cellular computation ultimately supporting human cognition. As a PhD candidate, your research will aim to uncover the cellular and molecular mechanisms underlying fast electrical signaling in human cortical neurons.

The project is funded by an ERC advanced grant awarded to Prof.dr. Huib Mansvelder: https://inf.cncr.nl/research_teams/

Your duties
During the research you use the following approach:

• You culture human iPSC-derived neurons and organotypic slices of human brain tissue
• You use CRISPRa/CRISPRi tools to manipulate target genes in human neurons, both iPSC-derived and in organotypic slice cultures of human brain tissue
• you study electrophysiological recordings and analysis from human (iPSC-derived) neurons in cultures
• you perform biochemical, transcriptomic and immunohistological analyses of expression in human neurons

Our lab is a part of an inspiring academic environment. In addition to your research, you have an opportunity to participate in teaching. You may also be involved in supervising Bachelor and Master students. You will become a member of the ONWAR graduate school (https://www.onwar.nl).

Relevant references:

1. Large and fast human pyramidal neurons associate with intelligence. (2018) Goriounova NA, Heyer DB, Wilbers R, …, Mansvelder HD. Elife. 2018. doi: 10.7554/eLife.41714.
2. Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling (2023) René Wilbers, …, Huibert D. Mansvelder, Natalia A. Goriounova. BioRxiv 2022.11.29.518317; doi: https://doi.org/10.1101/2022.11.29.518317
3. Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks. (2022) Mossink B, …, Schubert D, Nadif Kasri N. Mol Psychiatry. 2022 Jan;27(1):1-18. doi: 10.1038/s41380-021-01117-x.
4. Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance (2022) Page et al., Proc Natl Acad Sci U S A. 2022 Jan 18;119(3):e2109395119. doi: 10.1073/pnas.2109395119.
5. Genes, Cells and Brain Areas of Intelligence. Goriounova NA, Mansvelder HD. Front Hum Neurosci (2019). doi: 10.3389/fnhum.2019.00044.

• you have a MSc degree in Molecular/Cellular Neuroscience
• you have prior experience with culturing human iPSC-derived neurons/organoids
• you have prior experience using CRISPRa/CRISPRi or other RNAi tools
• you have excellent communication and writing skills in English
• prior experience in cellular electrophysiology (patch clamp) is an asset
• programming and data analysis skills (Matlab, Python) are an asset
• you have a strong motivation to pursue a research career

The project is planned to start in September/October 2023.

A challenging position in a socially involved organization. You will be part of a collaborative, enthusiastic team consisting of multiple PhD-students and experienced post-docs in which we collectively work on important research questions. The salary will be in accordance with Dutch university regulations for academic personnel and amounts € 2.541 per month during the first year and increases to € 3.247 per month during the fourth year, based on a full-time employment. The job profile (PhD candidate) is based on the university job ranking system and is vacant for 1 FTE.

The appointment will initially be for 1 year. After a satisfactory evaluation of the initial appointment, the contract will be extended for a total duration of 4 years.

Additionally, the VU Amsterdam offers excellent fringe benefits and various schemes and regulations to promote a good work/life balance, such as:

• 8% holiday allowance and 8.3% end-of-year bonus
• contribution to commuting expenses
• optional model for designing a personalized benefits package

Vrije Universiteit Amsterdam

The ambition of Vrije Universiteit Amsterdam is clear: to contribute to a better world through outstanding education and ground-breaking research. We strive to be a university where personal development and commitment to society play a leading role. A university where people from different disciplines and backgrounds collaborate to achieve innovations and to generate new knowledge. Our teaching and research encompass the entire spectrum of academic endeavor - from the humanities, the social sciences and the natural sciences through to the life sciences and the medical sciences.

Vrije Universiteit Amsterdam is home to more than 30,000 students. We employ over 5,500 individuals. The VU campus is easily accessible and located in the heart of Amsterdam's Zuidas district, a truly inspiring environment for teaching and research.

Diversity
We are an inclusive university community. Diversity is one of our most important values. We believe that engaging in international activities and welcoming students and staff from a wide variety of backgrounds enhances the quality of our education and research. We are always looking for people who can enrich our world with their own unique perspectives and experiences.

The Faculty of Science
Working at the Faculty of Science means working together with students, PhD candidates and scientists who are focused on their discipline, yet also have a broad view of the world. We are proud of the collegial working environment within the faculty, which is characterised by an ambitious and pragmatic attitude with commitment to the bigger picture. At the Faculty of Science, scientists and students work on fundamental and complex social issues for a sustainable and healthy future. From forest fires to big data, from obesity to malnutrition, from genetics to pharmaceuticals and from molecules to the moon: our teaching and research cover the full breadth of the natural sciences. Scientific teaching and research is highly experimental, technical, computational and interdisciplinary in nature. This is why we collaborate extensively with leading research institutes and industry. The faculty has over 11,000 students studying across 40 educational programmes and employs over 1,600 staff spread over 10 scientific departments, making us the largest science faculty in the Netherlands.

Center for Neurogenomics and Cognitive Research (CNCR)

CNCR includes the Department of Neurosciences at the Faculty of Sciences. The CNCR is a vibrant scientific environment that generates integrated research programs from genes to behavior, each combining mouse and human studies (https://cncr.nl/). In our center, 150 people work closely together in defining how in essence simple molecular and cellular processes shape the emergent complexity of the brain.

We have the specific ambition to unravel the mechanisms by which brain cells and circuitry act both in health and disease. We aim to translate mechanistic knowledge into understanding of (dys)function of the human brain. Our neuroscience research area covers analysis over many spatial levels, from genes to the intact organism, and over a large temporal scale, from microsecond molecular events to the years of functioning of the human brain.