M.Sc. internship: Using Human Induced Pluripotent Stem Cells and Neural Models to Explore the Genetics of Human Speech and Language

Job description

We are looking for intern(s) to contribute to research investigating molecular mechanisms and biological pathways that go awry in neurodevelopmental disorders with prominent speech impairments starting in September or October 2025 (exact date can be adjusted).

Our research involves investigating rare gene disruptions known to cause speech and language disorders in neurodevelopmental syndromes. By exploring the effects of these disruptions (such as in FOXP1/2/4, CHD3, SETBP1 among other genes) in human cell models cultivated in our lab, we aim to understand the underpinning mechanisms of these disorders. We not only generate neurons from healthy and mutant induced pluripotent stem cells (iPSCs) in 2D or 3D culture systems, but also seek to uncover how these disruptions lead to speech-impairing developmental diseases.

Besides developing key laboratory skills in cell and molecular biology, you will be exposed to essentials of team work, gain experience in documenting your results in oral and written forms, and seeking useful feedback in a scientific setting. As an important part of our research team, you will not only gain robust scientific skills but also invaluable experience in a collaborative research environment. Join us, and let's explore the genetic mysteries of human communication together!

Project 1: Deciphering the neurobiological pathways involved in heterogeneous SETBP1-haploinsufficiency disorder using human brain organoids

Daily supervisor: Dr. Maggie Wong (post-doc) 

Internship Supervisor: Prof. Dr. Simon E Fisher

In this internship, you will be involved in on-going projects that investigate the function of SETBP1 and the disease mechanisms underlying SETBP1-haploinsufficiency disorder where speech and language impairment, wide-range of intellectual functioning, behavioural problems, and motor delays are central clinical features. You will perform systemic characterization of cerebral organoids grown from SETBP1-knockout iPSCs that we previously generated and patient-derived iPSCs, using immunostaining, high-throughput microscopy using slidescanner and/or confocal microscope. You will learn to perform extensive image analysis with existing in-house macros, and help implementing new image analysis pipelines. These analyses are complementary to our transcriptomic profiling of these organoids at bulk and single-cell level. You will also perform immunoblotting to assess the alterations of signaling pathways based on the results of our transcriptomic analyses. You will work under the daily supervision of Dr. Wong and closely with a research assistant.

Preferred skills: experience with microscopy, image analysis and basic molecular biology techniques, familiarity with R, Python, Matlab or FIJI/ImageJ is a plus. Candidates who only match with some of the skills are also strongly encouraged to apply.

Project 2: Culturing and characterizing induced pluripotent stem cells (iPSCs) with speech-related gene mutations

Daily supervisor: Dr. Fatma Uzbas (post-doc)

Internship Supervisor: Prof. Dr. Simon E Fisher

In this internship, you will acquire hands-on experience in culturing and characterizing human induced pluripotent stem cells (iPSCs) with speech-related gene variants. You will learn how to assess their genomic integrity, along with evaluating their pluripotency status using immunocytochemistry and quantitative real-time PCR (qPCR). The internship will further develop your competencies in cell fixation, staining procedures, and imaging using epi-fluorescence or confocal microscopy. Furthermore, your training may involve extracting RNA from cells, performing reverse transcription reactions for cDNA synthesis, running qPCR, and analyzing the results. Based on the progress, you may have the chance to ultimately test the organoid-forming capacity of the characterized cell lines.

Preferred skills: Basic experience in aseptic technique and cell culture; familiarity with molecular biology techniques; fundamental understanding of immunocytochemistry and microscopy.

Project 3: Implementing a protocol for generating thalamic organoids from human iPSC lines

Daily supervisor: Dr. Fatma Uzbas (post-doc)

Internship Supervisor: Prof. Dr. Simon E Fisher

In this internship, you will acquire hands-on experience in culturing human induced pluripotent stem cells (iPSCs) and implementing a protocol to generate thalamic organoids from these lines. Your initial training will focus on maintaining high-quality iPSCs cultures, including expanding and freeze-thawing appropriately. Together with your daily supervisor, you will then establish and optimize a method to generate thalamic organoids based on the published protocols. This will involve comparing alternative protocols, fine-tuning experimental conditions, and troubleshooting challenges in organoid initiation and maintenance. Based on the progress, you may also be involved in the downstream analyses, such as fixing, staining, and imaging the organoids with confocal microscopy; extracting RNA for cDNA synthesis and qPCR, and interpreting the results.

Preferred skills: Hands-on experience in human cell culture (crucial), familiarity with molecular biology techniques and microscopy.

Application procedure

• To apply, please submit the following pdf documents via this link on our application portal:
  • a brief statement outlining your motivation
  • your CV
  • the name of project(s) you wish to apply for
• The deadline for applications is 4 July 2025.
• Internships have to be self-funded and should last at least 5 months. 

• If you have questions about this internship opportunity that you wish to discuss before applying, please get in touch with maggie.wong [at] mpi.nl (maggie[dot]wong[at]mpi[dot]nl), fatma.uzbas [at] mpi.nl (fatma[dot]uzbas[at]mpi[dot]nl), or secretariat.genetics [at] mpi.nl (secretariat[dot]genetics[at]mpi[dot]nl)