PhD Position on the Cell-Specific Regulations of leptinotarsin

PhD position (Gene Regulation & Evolution): Studying Evolution of cell-specific regulations of a neurotoxin and its self-resistance

 Thinking of doing your PhD in the Life Sciences? The PhD Programme „Gene Regulation in Evolution“ (GenEvo) is offering talented, young scientists the chance to work on cutting edge research projects. As a GenEvo PhD student, you will join a community of exceptional scientists working together on the core question of how complex and multi-layered gene regulatory systems have evolved.

Activities and responsibilities:

In the field of “Gene Regulation & Evolution”, Shuging Xu, Marion Silies and Claudia Keller Valsecchi offer the following PhD project:

Studying Evolution of cell-specific regulations of a neurotoxin and its self-resistance

Many insects produce toxins in their hemolymph that are lethal to their predators but not to themselves (1). To achieve this, insects must specifically regulate the production of the toxins and evolve self-resistance at the cellular level. However, the underlying mechanisms and evolutionary processes remain largely unknown.

PhD Project: Studying Evolution of cell-specific regulations of a neurotoxin and its self-resistance

Leptinotarsa hemolymph produces a high abundance of leptinotarsin, a presynaptic neurotoxin that is lethal to many insects and vertebrates but harmless for the carriers (2, 3). The peptide suggests that the toxin evolved from a duplicated juvenile hormone esterase (JHE), which is specifically expressed in hemolymph (4). While the regulation of JHE is age-dependent (5), leptinotarsin is found in all developmental stages. Our preliminary data suggest that leptinotarsin is produced in a specific type of hemocyte cells, suggesting the evolution of new gene regulations of leptinotarsin. Here, we will use tools from comparative genomics and single-cell sequencing to study the mechanisms and evolution of cell-specific regulations of leptinotarsin. In addition, we will investigate the mechanisms of toxin self-resistance using a functional neurobiology approach. Specifically, we will address three questions:

1) Which cells produce leptinotarsin and how is it regulated at the cellular level?
2) What are the mechanisms of the leptinotarsin self-resistance?
3) How did leptinotarsin and its resistance mechanism evolve?

We will first perform single-cell RNA-sequencing (scRNA-seq) on Colorado potato beetle (Leptinotarsa decemlineata) hemocytes to characterize the cellular regulations of leptinotarsin (Aim 1). We will further use single-cell ATAC-sequencing to investigate how chromatin structures contribute to the evolution of cell-specific regulations of leptinotarsin. Second, we will investigate possible mechanisms of leptinotarsin self-resistance by investigating synaptic targets of leptinotarsin in Drosophila (Aim 2). Third, we will retrace the evolutionary history of leptinotarsin and the toxin self-resistance mechanisms by analyzing the genomes of closely related Leptinotarsa species and other insects (Aim 3). Comparing the target molecules in species that are susceptible to the toxin with resistant species will provide insights into the evolution of resistance mechanisms. We hypothesize that leptinotarsin evolved new regulations via changing cell-specific chromatin accessibility, the process of which is after the emergence of self-tolerance. Together, this project will provide new insights into the evolution of novel gene regulatory networks at the single-cell level.

The PhD student and project will be conducted under the joint supervision of Prof Shuqing Xu and Prof Marion Silies. This project will further benefit from expertise of Dr. Claudia Keller Valsecchi on the mechanism of epigenetic regulations.

What we offer:

·       Exciting, interdisciplinary projects in a vividly international environment, with English as our working language

·       Advanced training in scientific techniques and professional skills

·       Access to state-of-the-art Core Facilities and their technical expertise

·       14 fully funded positions with financing until the completion of your thesis

·       A lively community of 24 PhD students supported by 25 Principle Investigators

·       Collaboration with the International PhD Programme (IPP) at IMB with more than 150 PhD students from 40 different countries

Requirements:

Are you an ambitious, young scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining GenEvo is your opportunity to give your scientific career a flying start!

All you need is:

·       Master or equivalent

·       Interactive personality & good command of English

·       2 letters of reference

For more details on the projects offered and how to apply via our online form, please visit www.genevo-rtg.de/application.

The deadline for applications is 27 January 2022. Interviews will take place 04-06 April 2022.