This year’s applications were so outstanding, that the DIGS-BB Steering Committee had a very difficult time selecting candidates from the 15 nominations. And eventually all seven candidates who were invited to defend their application in a chalk talk were given a DIGS-BB Fellow Award 2023:
- Jiffin Benjamin (Michael Sieweke Group)
- Nora Bölicke (Mareike Albert Group)
- Brett Emery (Hayder Amin Group)
- Manavi Jain (Frank Buchholz Group)
- Palina Nepachalovich (Maria Fedorova Group)
- Hà Ngọc Anh Nguyễn (James Sáenz Group)
- Sarah Speed (Elisha Krieg Group)
The award honours outstanding PhD students after the 1st year of thesis work and includes a price money of €2,000. It aims to help their research work, development of research skills, and to strengthen their research network. The allowance can be used to cover project consumables, attendance to workshops and conferences, research visits to collaborators’ labs, as well as to cover cost for a side project.
An outstanding performance during the 1st year of PhD work, along with a nomination and justification by their Thesis Advisory Committee (TAC) in the 1st AR TAC meeting is required to be eligible for the award. The students presented the current state of their thesis work to the DIGS-BB Steering Committee in writing. Applications positively evaluated were invited to defend their application in a chalk talk before the committee. Detailed information on that work can be found below.
Macrophages play a crucial role in the body, with functions ranging from phagocytosis and antigen presentation to tissue remodeling and wound healing. Despite their potential in cell therapeutics, the limited proliferative capacity of most macrophages in culture has hindered progress in their applications. However, studies from our group point towards a mechanism of self-renewal in macrophages that preserves their functionality, presenting an opportunity for personalized cell therapeutics. To this end, my project aims to develop a cost-effective and readily accessible method for using human donor-derived macrophages for cell therapeutics, utilizing small molecule compounds to activate self-renewal pathways. Employing human iPSC-derived macrophages for high-throughput drug screening, I am identifying compounds that promote self-renewal while studying their effects on macrophage function. My ultimate goal is to establish a proof-of-concept for cell therapeutic applications in neonates by expanding fetal macrophages from the human placenta.
The neocortex is considered to be one of the key advancements enabling higher cognitive abilities. Its development starts from a sheet of neural progenitor cells (NPCs), most of which eventually give rise to neurons. Throughout evolution the neocortex has undergone significant expansion along the human lineage. This increase in size is hypothesized to be caused by differences in NPC abundance and proliferative potential among species, that eventually result in higher neuronal output in humans. Cell fate determination of NPCs is guided by precise temporal and spatial gene expression profiles that are in turn driven by epigenetic mechanisms including Polycomb group (PcG) regulation. PcG proteins are a group of epigenetic modifiers that catalyze repressive post-translational histone modifications. One of the major PcG complexes is the Polycomb repressive complex 2 (PRC2) that mediates methylation of lysine 27 of histone 3. Impaired PRC2-regulation in humans has been associated with neurodevelopmental disorders affecting brain size. Moreover, studies in mouse models have implicated PRC2 in controlling various stages of cortex development including the expansion and differentiation of NPCs. These findings render PcG proteins potential contributors to the evolutionary expansion of the cortex. The specific mechanisms mediating PcG-associated transcriptional repression especially in humans remain incompletely understood and are an active field of research. The aim of my PhD thesis is to examine the role of PRC2 in human neocortex development and neurodevelopmental disorders using cortical organoids.
Information processing in the brain occurs at multiple spatial and temporal scales, through combinations of transcriptional regulation and oscillatory neural activity patterns. Each scale produces specific information, where together they coordinate to provide the foundation of diverse cognitive functions and behaviors. To examine hippocampal network dynamics in healthy states and disruptive states such as development, aging, or disease, I am exploiting the large-scale coordination between electrophysiological, morphological, and gene expression information. Therefore, my project aims to build a multi-scale platform utilizing high-density biosensors and spatial transcriptomics to create both a functional and transcriptomic map of hippocampal network dynamics in both health and disease states.
ß-Hemoglobinopathies are the most common monogenic disorders resulting in either sickle cell disease or ß-thalassemia. The only curative option available is allogenic hematopoietic stem cell transplantation; however, it is severely limited by the availability of matched donors and the risk of immunological complications. Transplantation of genetically modified autologous hematopoietic stem cells provides a promising alternative for patients lacking compatible donors. Patients with a congenital increase in fetal hemoglobin (HbF) expression after birth have a much milder course of disease. For my project, I want to use site-specific recombinases (SSRs) as a gene editing tool to achieve targeted reactivation of HbF by knocking out its transcriptional repressor BCL11A gene. SSRs can catalyse specific DNA rearrangements between two target sites resulting in a predictable and accurate editing outcome. I have evolved designer recombinases specific for excising a piece of BCL11A gene. Through the course of my PhD, I will characterize and optimize activity and specificity of the desired variants for developing a gene therapy based curative treatment.
In our group, we work on conceptualizing a lipid quality control (LQC) machinery, which, like a maintenance team, ensures the proper composition and function of the cellular lipidome. In comparison to relatively well-studied protein or DNA quality control systems, LQC is much less investigated, but we envision it as a set of mechanisms activated in various biological contexts to keep lipidome in homeostasis. For example, oxidative stress, common for many pathologies from atherosclerosis to cancer, is accompanied by oxidative damage to plasma membrane lipids, which compromises cell integrity. And the goal of my project is to find out which LQC mechanisms, in addition to the well-recognized system of antioxidants and redox enzymes, contribute to counteracting lipid oxidation-mediated cell death.
Hà Ngọc Anh Nguyễn
How do lipids impact cell membrane design principles? Sterols, like cholesterol, have been considered crucial for the Eukaryotic membrane due to their ability to modulate biophysical properties and organize membranes through lipid rafts. Some bacterium, however, employs a diverse panel of hopanoids, a family of compounds, each different but with functional similarities to cholesterol. These two diverging systems are crucial in their respective organisms, yet the extent of their membrane-modulating capacity has never been directly compared in a living model membrane system. In this research, I utilized *Mesoplasma florum* to examine the comparative roles of sterols and hopanoids. By dissecting membrane properties modified by cholesterol and hopanoid species, I hope to understand the physiological relevance of specific biophysical traits and how they influence membrane design principles.
My PhD work combines the fields of DNA nanotechnology and synthetic materials to create DNA-functionalized polymers for use in sequencing diagnostics. The combination of the tunable nature of polymer backbones and the programmable nature of DNA oligonucleotides has greatly expanded the design space for soft materials engineering, offering exceptional control over material properties at the nanoscale. In the Krieg group, we engineer programmable nanomaterials based on a methanol-responsive polymer (MeRPy), which consists of long linear chains of polyacrylamide grafted with DNA oligonucleotide anchors. The main objective of my PhD research is to streamline next-generation sequencing (NGS) workflows by engineering MeRPy as a novel platform for enhanced sequencing library preparation. Ultimately, I envision the MeRPy platform as a low-cost, open-source solution for sequencing pathogens in resource-limited areas to enable more expedited disease diagnosis and transmission tracking.