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Cha­rité - Uni­ver­si­täts­me­di­zin Ber­lin

The Char­ité - Uni­versitätsmed­izin Ber­lin is a joint med­ical fac­ulty, which serves both Freie Uni­versität Ber­lin and Hum­boldt Uni­versität zu Ber­lin. As one of the largest uni­versity hos­pit­als in Europe with an import­ant his­tory, it plays a lead­ing role in research, teach­ing and clin­ical care. The Char­ité uni­versity hos­pital has also made a name for itself as a mod­ern busi­ness with cer­ti­fic­a­tions in the med­ical, clin­ical and man­age­ment fields.

research assist­ant / PhD stu­dent

Insti­tut für Kli­ni­sche Phy­sio­lo­gie/AB Ernäh­rungs­me­di­zin, Med. Kli­nik f. Gas­tro­ent., Infekt. & Rheu­mat., CC13

Work­ing field:

PhD stu­dent Pos­i­tion - life sci­ence
Molecu­lar archi­tec­ture of tight junc­tions and para­cel­lu­lar ion chan­nels

Require­ments: Mas­ter degree in bio­chem­istry, bio­logy, bioin­form­at­ics, bio­tech­no­logy or a related field of study and a strong interest in struc­tural and func­tional cell bio­logy.
We offer a strong, com­mit­ted and enthu­si­astic sci­entific envir­on­ment at the inter­face between basic and pre­clin­ical research. Optional: Asso­ci­ation with DFG Research Train­ing Group "TJ-Train", GRK 2318 (http://klinphys.charite.de/grk).

Tight Junc­tions reg­u­late para­cel­lu­lar per­meab­il­ity for solutes and water in epi­thelia and endothelia and are essen­tial for tis­sue bar­ri­ers. On the one hand, tran­si­ent open­ing of tight junc­tions could improve drug deliv­ery across tis­sue bar­ri­ers, e.g. the intest­inal epi­the­lium or the blood brain bar­rier. On the other hand, sta­bil­iz­a­tion of patho­lo­gic­ally altered tight junc­tions could recover the pro­tect­ive func­tion of a com­prom­ised tis­sue bar­rier (e.g. in inflam­mat­ory bowel dis­ease). To achieve this, the trans­mem­brane claudin pro­teins are prom­ising tar­gets, since they form the back­bone of tight junc­tions and determ­ine their para­cel­lu­lar bar­rier prop­er­ties.
In the pro­ject, claudin struc­ture-func­tion rela­tion­ships will be char­ac­ter­ized to elu­cid­ate the molecu­lar mech­an­ism of para­cel­lu­lar per­meab­il­ity reg­u­la­tion by claud­ins. Aim is, in par­tic­u­lar, to cla­rify the molecu­lar archi­tec­ture of tight junc­tions and how claud­ins inter­act with each other at cell-cell con­tacts to form intramem­bran­ous poly­mers which – in a claudin sub­typ-depend­ent man­ner – either tighten the para­cel­lu­lar gap or form size- and charge-select­ive chan­nels.
The fol­low­ing meth­ods will be applied: (a) exper­i­mental: cell cul­ture, trans­fec­tion, cel­lu­lar recon­sti­t­u­tion von tigh junc­tion strands/poly­mers, con­focal and STED super res­ol­u­tion micro­scopy, live cell ima­ging, FRET, FRAP, site-dir­ec­ted muta­gen­esis, freeze-frac­ture elec­tron micro­scopy, West­ern blot, chem­ical pro­tein cross­link­ing, meas­ure­ment of para­cel­lu­lar ion- and tracer per­meab­il­ity; (b) struc­tural bioin­form­at­ics: homo­logy mod­el­ing of claudin pro­tein struc­tures, oli­gomer dock­ing and espe­cially molecu­lar dynam­ics sim­u­la­tions of mem­brane- embed­ded claudin oli­gomers.

Require­ments:

Require­ments:Very good Mas­ter degree in bio­chem­istry, bio­logy, bioin­form­at­ics, bio­tech­no­logy or a related field of study and a strong interest in struc­tural and func­tional cell bio­logy.
We offer a strong, com­mit­ted and enthu­si­astic sci­entific envir­on­ment at the inter­face between basic and pre­clin­ical research.

For more Inform­a­tion, con­tact joerg.piontek@charite.de, see https://klinphys.charite.de and pro­ject-related pub­lic­a­tions:

1. Hempel et al., 2020. Assembly of Tight Junc­tion Strands: Claudin-10b and Claudin-3 Form Homo Tet­ra­meric Build­ing Blocks that Poly­mer­ise in a Chan­nel-Inde­pend­ent Man­ner. J Mol Biol. pii: S0022-2836(20)30222-9. doi: 10.1016/j.jmb.2020.02.034
2. Pion­tek et el., 2020. Molecu­lar archi­tec­ture and assembly of the tight junc­tion back­bone. Biochim Bio­phys Acta., 1862(7):183279. doi: 10.1016/j.bbamem.2020
3. Rosenthal et al., 2019. Claudin-15 forms a water chan­nel through the tight junc­tion with dis­tinct func­tion com­pared to claudin-2. Acta Physiol (Oxf). 228(1):e13334. doi: 10.1111/apha.13334
4. Neuhaus et al., 2018. Revers­ible open­ing of the blood-brain bar­rier by claudin-5-bind­ing vari­ants of Clostridium per­frin­gens entero­toxin's claudin-bind­ing domain. Bio­ma­ter­i­als 161: 129-143
5. Pion­tek et al., 2008. Form­a­tion of tight junc­tion: determ­in­ants of homo­philic inter­ac­tion between clas­sic claud­ins. FASEB J. 22:146-158
Sci­entific staff is given suf­fi­cient time to carry out their own sci­entific work in accord­ance with their employ­ment rela­tion­ship.