Dr. Vibor Laketa

Infectious Diseases Imaging Platform (IDIP)

In CIID, we aim to achieve a com­pre­hen­sive under­stand­ing of the phys­i­ol­o­gy of major human pathogens and to devel­op improved ther­a­peu­tic strate­gies through advanced microscopy-based mol­e­c­u­lar imag­ing, which can iden­ti­fy and quan­ti­ta­tive­ly ana­lyze indi­vid­ual mol­e­c­u­lar events under­ly­ing dif­fer­ent patho­phys­i­o­log­i­cal states. Tra­di­tion­al bio­chem­i­cal, genet­ic, and “omics” approach­es have pro­vid­ed valu­able insights into host–pathogen inter­ac­tions, but they are large­ly pop­u­la­tion-based, end-point analy­ses. Such meth­ods often obscure rare or sto­chas­tic mol­e­c­u­lar events by aver­ag­ing them out. Yet these indi­vid­ual events are pre­cise­ly what dri­ve the tran­si­tion between healthy and dis­eased states. We believe that to tru­ly under­stand dif­fer­ent phys­i­o­log­i­cal states, we need to employ a reduc­tion­ist exper­i­men­tal approach that is able to cap­ture and quan­ti­ta­tive­ly exam­ine these indi­vid­ual mol­e­c­u­lar events. Such infor­ma­tion can then be incor­po­rat­ed into math­e­mat­i­cal mod­els togeth­er with the obser­va­tions made using the pop­u­la­tion-based approach­es ulti­mate­ly lead­ing to a com­pre­hen­sive under­stand­ing of the under­ly­ing patho-phys­i­o­log­i­cal processes.

Due to recent inno­va­tions, the only method­ol­o­gy able to cap­ture and quan­ti­ta­tive­ly exam­ine indi­vid­ual mol­e­c­u­lar events in a com­plex bio­log­i­cal sys­tem is microscopy-based imag­ing. A micro­scope is unique in being able to:

  • show how “stuff” looks like (spa­tial orga­ni­za­tion of the liv­ing mat­ter — mol­e­cules, organelles, cells, pathogens etc..)
  • tell us how much “stuff” is where
  • and how all this changes over time in a liv­ing system

A mod­ern micro­scope is a robot that can sam­ple com­plex dynam­ics of a bio­log­i­cal sys­tem across a wide range of spa­tiotem­po­ral scales and orga­ni­za­tion­al lev­els of com­plex­i­ty, and thus is able to pro­vide the most real­is­tic rep­re­sen­ta­tion of a liv­ing sys­tem. It is a big tech­ni­cal chal­lenge to observe and quan­ti­fy these sto­chas­tic mol­e­c­u­lar events. An equal­ly big chal­lenge is to under­stand how they give rise to dif­fer­ent stereo­typ­i­cal patho-phys­i­o­log­i­cal states that we observe in “bulk” mea­sure­ments. In this respect, microscopy-based analy­sis yields quan­ti­ta­tive infor­ma­tion that can be inte­grat­ed into pre­dic­tive mul­ti­scale math­e­mat­i­cal mod­els of infec­tion that will ulti­mate­ly be used to rec­on­cile the find­ings obtained by the reduc­tion­ist approach with the ones that are based on pop­u­la­tion measurements.

The Infec­tious Dis­eases Imag­ing Plat­form (IDIP) pro­vides, devel­ops and applies high-end microscopy infra­struc­ture under enhanced biosafe­ty con­tain­ment 2 and 3 con­di­tions (BSL‑2 and 3) to enable infec­tious dis­eases research.

Over 250m2 of ground (BSL‑2) and under­ground (BSL‑3) area of the CIID is ded­i­cat­ed to IDIP infra­struc­ture which is organ­ised in 14 inter­con­nect­ed microscopy rooms, tis­sue cul­ture and sam­ple prepa­ra­tion, image analy­sis and office areas. IDIP imple­ments a com­pre­hen­sive range of bioimag­ing tech­nolo­gies that allow infec­tious dis­ease research across vast­ly dif­fer­ent spa­tiotem­po­ral scales and orga­ni­za­tion­al com­plex­i­ties, going from struc­tur­al stud­ies on macro­mol­e­c­u­lar scale all the way to whole organ/body imag­ing in liv­ing ani­mals. More infor­ma­tion about IDIP organ­i­sa­tion and instru­men­ta­tion can be found on the IDIP home­page https://www.idip-heidelberg.org/.