Description
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta cells inthe Islets of Langerhans in the pancreas. While a cure is absent and the initial trigger(s) are not
known, invasive insulin therapy is a lifesaver for (T1D) for over 100 years, albeit way less effective
in controlling blood glucose compared to the beta cells. To study the disease using specialized
techniques in labs all over the world the nPOD biobank (network for pancreas donors with T1D;
jdrfnpod.org) has been initiated. We apply routine large-scale EM (nano-anatomy; nanotomy;
nanotomy.org) on nPOD pancreas and built an EM database of the biobanked biomaterial.
Nanotomy is now a routine technique in our facility: scanning entire EM sections at high resolution,
comparable to scanners for histology. However, analysis is limited to the interpretation of the grey
scale data. Correlated microscopy (fluorescence microscopy and EM) allows biological processes
and/or cellular building blocks to be identified and dynamically studied followed by ultrastructural
analysis, but the resolution of LM and EM do not match [1]. As an alternative, we optimized
elemental dispersive X-ray analysis (EDX, ‘ColorEM’) to revisit areas of interest in the nanotomy
maps, which we now also routinely use to identify endogenous structures, paint structures or label
molecules based on elemental composition. All identification techniques above typically aid in
identifying structures in large-scale EM maps and therefore their broad implementation will be
highly useful in core facilities. In T1D research, these technique revealed anomalies in exocrine/
endocrine cells in (pre)diabetic patients [2]. Moreover, others found a diminished pancreas weight
in (pre)diabetic patients, also hinting on a role of the exocrine pancreas in development of T1D [3].
However, a cause-consequence relationship could not be defined. Therefore, we now established
a zebrafish larvae model to monitor in real time how stress in the Islets of Langerhans may be
altered when modulating the exocrine tissue, which may be an initial trigger that ultimately
destroys the insulin producing cells. Today, I will introduce the now routine techniques on
Correlated microscopy, Nanotomy, ColorEM and include probes that help to identify molecules of
interest. Moreover, I will highlight the benefit of an living model, the zebrafish larvae, for cell
modulation and analysis using fluorescence microscopy in research [4] and discuss how these
techniques may be further developed and implemented as valuable as generic tools for a broad
microscopy and biomedical community.
| Period | 4-Sept-2022 |
|---|---|
| Event title | 16th Multinational Congress on Microscopy |
| Event type | Conference |
| Location | Brno, Czech RepublicShow on map |
| Degree of Recognition | International |