Internship: HgNeuroDetox

HgNeuroDetox is a multidisciplinary project whose objective is the high-throughput discovery of promising compounds for mercury (Hg) detoxification with a major focus on the neurotoxic aspects of this contaminant.
It is well known that Hg forms stable adducts with sulfur (S) and selenium (Se)-containing compounds. It has also been observed that the detoxification mechanism against organomercurials and inorganic mercury in wild animals (bird, fish, rat) and even humans is based on the interaction of cysteine (Cys) and selenocysteine (Sec) of proteins and metabolites forming less toxic and more stable Hg forms which favor their body excretion. For this reason, we share the diffused hypothesis that thiol and selenol compounds could be exploited to plan efficient strategies counterattacking the environmental Hg toxicity. Although the scientific community has produced much evidence about the Hg detoxifying efficiency of natural and synthetic S- and Se-compounds, an unbiased High-Throughput Screening (HTS), to find lead compounds is still missing. We expect this approach would be more comprehensive and point to taking also into account the synergistic effects of multi-compound mixtures.
The most innovative contribution to the field is applying a system-biology-like approach to screen, evaluate, design, and validate lead compounds. The primary technical barrier to be lifted for the proposed HTS approach is the definition of robust molecular readouts to monitor the system perturbations induced by Hg and its detoxifying compounds in the nervous system.
In the framework of this project we will focus on hippocampal toxicity, studying the altered behavioural task associated with this nervous system compartment, which is reported as one of the main targets of Hg toxicity and thus a robust source of quantifiable parameters. Thus, our model will be a mouse hippocampal cell line HTT22 and mouse hippocampal tissues.
The goal of this Master degree stage is to find the molecular readouts in hippocampal neurons in cell culture exposed to methylmercury. The readouts could be protein expression changes, oxidative post translational modifications, mercury binding proteins. For the last parameter an innovative analytical method to detect mercury bounded proteins needs to be developed.

Responsibilities:
o Design and conduct mass spectrometry experiments (LC-MS/MS) to identify the protein target of mercury.
o Focus on thiol modifications and redox-active proteins.
o Sample preparation from cell culture.
o Develop and optimize methods to detect mercury protein target in standard protein and complex mixtures

Profile
Desired knowledge and skills: knowledge of protein chemistry, analytical chemistry, cell biology

Degree:
Master in Biochemistry, Analytical Chemistry, or Biology

Position available from:
February/March 2025 for 6 months, possible PhD fellowship after