Dr. Vibor Laketa

Vibor.Laketa
@med.uni-heidelberg.de
Phone: +49 6221 56–34410

Estab­lish­ment and Appli­ca­tion of
Advanced Microscopy Infrastructure

Projects

Microscopy and infec­tious dis­ease research have been insep­a­ra­ble part­ners ever since in the 1670s Anthonie van Leeuwen­hoek used his new­ly-invent­ed micro­scope to exam­ine a sam­ple of plaque he had scraped from his own teeth, and observed — for the first time — bac­te­ria and oth­er microor­gan­isms that share the world with us. Undoubt­ed­ly, microscopy was fun­da­men­tal in infec­tious dis­ease research, as it was nec­es­sary for the dis­cov­ery of infec­tious agents by direct obser­va­tion and lat­er on also for their diagnosis.

In mod­ern bio­med­ical research that is being real­ized in CIID, microscopy-based exper­i­men­tal approach has a cen­tral role. A com­pre­hen­sive under­stand­ing of host-pathogen inter­ac­tions requires quan­ti­ta­tive assess­ment of mol­e­c­u­lar events across a wide range of spa­tiotem­po­ral scales and orga­ni­za­tion­al com­plex­i­ties Due to recent tech­ni­cal devel­op­ments, this is cur­rent­ly only achiev­able with microscopy. Based on devel­op­ment of new imag­ing modal­i­ties, flu­o­res­cent probes and sen­sors, com­put­er tech­nol­o­gy, image analy­sis algo­rithms and new bio­log­i­cal mod­el sys­tem, the field of bio­log­i­cal microscopy is under­go­ing a rev­o­lu­tion. Only now we are start­ing to appre­ci­ate and make use of the full poten­tial of the microscopy-based exper­i­men­tal approach. Mod­ern micro­scopes have evolved into com­plex robot­ic instru­ments capa­ble of auto­mat­i­cal­ly inter­ro­gat­ing a wide range of bio­log­i­cal process­es at vast­ly dif­fer­ent spa­tiotem­po­ral scales and orga­ni­za­tion­al com­plex­i­ties, from struc­tur­al stud­ies on macro­mol­e­c­u­lar scale all the way to whole organ/body imag­ing in liv­ing animals.

We believe that mod­ern microscopy tech­nol­o­gy is cur­rent­ly unique­ly posi­tioned to pro­pel the infec­tious dis­ease research to a new fron­tier. For these rea­sons, we are estab­lish­ing and apply­ing advanced microscopy infra­struc­ture to allow infec­tious dis­ease research across the range of dif­fer­ent spa­tiotem­po­ral scales and orga­ni­za­tion­al complexities.

More infor­ma­tion about IDIP organ­i­sa­tion and instru­men­ta­tion can be found on the IDIP home­page https://www.idip-heidelberg.org/. If you would like to use the IDIP infra­struc­ture, please fol­low the instruc­tions at https://www.idip-heidelberg.org/usage-concept.

Microscopy Infrastructure under BSL2 and BSL3 Containment

IDIP projects cov­er all aspects nec­es­sary for the exe­cu­tion of the microscopy-based exper­i­men­tal approach in the con­text of infec­tious dis­eases research. Typ­i­cal­ly, projects are relat­ed to the fol­low­ing activities:

  • Imple­ment­ing, oper­at­ing and pro­vid­ing advanced microscopy and cell sort­ing infra­struc­ture under enhanced biosafe­ty con­di­tions (BSL‑2 and BSL‑3). You can find more infor­ma­tion on IDIP infra­struc­ture at https://www.idip-heidelberg.org/equipment

  • Con­sul­ta­tion dur­ing microscopy-based project plan­ning and exper­i­men­tal design.
    Col­lab­o­ra­tion with­in projects being exe­cut­ed in CIID.

  • Advice and sup­port in image pro­cess­ing, data visu­al­i­sa­tion and presentation.
    Devel­op­ment of data acqui­si­tion and analy­sis automa­tion workflows.

  • Coor­di­na­tion of microscopy infra­struc­ture invest­ments and sup­port for relat­ed grants applications.

  • Edu­ca­tion and train­ing in microscopy and microscopy-relat­ed subjects.

Development of microscopy-based assays for drug screening and diagnostics

The microscopy-based approach holds immense poten­tial in advanc­ing trans­la­tion­al research and rev­o­lu­tion­iz­ing drug screen­ing pipelines, as well as enhanc­ing the sen­si­tiv­i­ty, speci­fici­ty, and adapt­abil­i­ty of med­ical diag­nos­tic pro­ce­dures. In light of the con­tin­u­ous emer­gence of nov­el pathogens, the devel­op­ment of rapid­ly adapt­able sero­log­i­cal and diag­nos­tic assays to assess their impact on human health and soci­ety has become indis­pens­able. The advent of severe acute res­pi­ra­to­ry syn­drome coro­n­avirus 2 (SARS-CoV­‑2) has under­scored the ongo­ing chal­lenge of rapid­ly eval­u­at­ing the influ­ence of evolv­ing viral vari­ants on exist­ing immu­ni­ty, ther­a­peu­tic options, and vac­cines. To address this chal­lenge and estab­lish a uni­ver­sal­ly applic­a­ble method­ol­o­gy for prompt­ly address­ing emerg­ing infec­tions in the future, we are cur­rent­ly engaged in the devel­op­ment of an auto­mat­ed mul­ti­plex microscopy approach inte­grat­ed with machine learn­ing-based analy­sis. By har­ness­ing this inno­v­a­tive tech­nique, we aim to not only deci­pher the impact of emerg­ing pathogens on human health but also facil­i­tate the screen­ing and analy­sis of human ther­a­peu­tic mon­o­clon­al anti­bod­ies. We are active­ly engaged in col­lab­o­ra­tive ini­tia­tives with the CIID and the Ger­man Cen­ter for Infec­tion Research (Deutsches Zen­trum für Infek­tions­forschung (DZIF)), where we are joint­ly work­ing on the devel­op­ment of microscopy-based assays address­ing diverse projects and a wide range of pathogens.