Rese­arch Inte­rests

Our lab is inte­res­ted in under­stan­ding the inter­play bet­ween innate immu­nity and human patho­ge­nic viruses. 

Key ques­ti­ons are:
•    What is the mole­cu­lar basis of anti-​viralinnate immune respon­ses? 
•    How does an orga­nism return to immune homeo­sta­sis after virus eli­mi­na­tion? 
•    Why can viruses still repli­cate in the pre­sence of a func­tio­nal innate immune sys­tem? 
•    What are the weak­ne­s­ses of viruses?
•    How can we streng­then our innate immune defen­ces against inva­ding viruses?

To under­stand com­mon prin­ci­ples and dif­fe­ren­ces, we study various viruses, inclu­ding# HIV, SARS-​CoV-2, IAV, MeV, EMCV and ZIKV.

1.    Con­trol of innate immune acti­va­tion and ter­mi­na­tion
Rapid acti­va­tion of innate immune respon­ses upon detec­tion of a patho­gen is cru­cial for effec­tive anti-​viral respon­ses. Howe­ver, pro­lon­ged or exces­sive acti­va­tion of innate immu­nity has patho­ge­nic con­se­quen­ces. Thus, pre­cise acti­va­tion of innate sen­sors and effi­ci­ent signal ter­mi­na­tion is cru­cial. Recently, we iden­ti­fied that two - not just one – dan­ger signals are requi­red to gua­ran­tee spe­ci­fic reco­gni­tion of RNA viruses (Ach­a­rya et al, Cell, 2022). Currently, we are aiming to under­stand which pro­te­ins play a key role in pre­venting exces­sive and/or chro­nic inter­fe­ron acti­va­tion using auto-​inflammatory disea­ses as models. In addi­tion, we define con­se­quen­ces of the ‘after­math’ of a battle bet­ween the innate immune sys­tem and viruses i.e. how cells return to a pre-​activated state.

2.    Viral mani­pu­la­tion of innate immu­nity
To repli­cate in the pre­sence of func­tio­ning innate immune respon­ses suc­cess­ful viruses have evol­ved stra­te­gies to mani­pu­late and evade anti-​viral defence mecha­nisms. We have recently iden­ti­fied stra­te­gies that allow SARS-​CoV-2 to coun­ter­act (Thoms et al, Sci­ence, 2020; Hayn et al, Cell Reports, 2021) or even exploit fac­tors of innate immu­nity (Prelli Bozzo et al, Nature Com­mu­ni­ca­ti­ons, 2021). Importantly, these stu­dies also revea­led remai­ning vul­nera­bi­li­ties of viral patho­gens against tar­ge­ted innate immune acti­va­tion (Hayn et al, Cell Reports, 2021). Currently, we are work­ing to under­stand how innate immune mani­pu­la­tion evol­ves in a recent zoo­no­tic virus (SARS-​CoV-2) that adapts to the human host and are aiming to iden­tify gaps in the innate immune eva­sion of other important human patho­gens, like HIV and IAV.
 
3.    Modu­la­tion of innate immu­nity as the­ra­peu­tic approach against viral and inflam­ma­tory disea­ses
Well balan­ced acti­va­tion of innate immu­nity may allow to con­trol viral patho­gens wit­hout caus­ing harm­ful inflam­ma­tion. Thus, we are aiming to iden­tify and cha­rac­te­rize novel immu­n­o­mo­du­la­tory pep­ti­des from the human pep­ti­dome. To this end, we are ana­ly­sing large libra­ries deri­ved from various human sources for their impact on innate immune acti­vity. Iden­ti­fied immu­n­o­mo­du­la­tory pep­ti­des can be fur­ther deve­lo­ped for the­ra­peu­tic anti-​viral and anti-​inflammatory approa­ches. Stu­dy­ing their phy­sio­lo­gi­cal role will pro­vide new insights into the regu­la­tion of innate immune respon­ses.

Recent key publi­ca­ti­ons
Full list: scho­lar.google.com/cita­ti­ons

  1. Ach­a­rya D, Reis R, Volcic M, Liu G, Wang MK, Chia BS, Nchioua R, Groß R, Münch J, Kirch­hoff F, Spar­rer KMJ*, Gack MU*. Actin cyto­ske­le­ton remo­de­ling pri­mes RIG-​I-like recep­tor acti­va­tion. Cell. 2022 Sep 15;185(19):3588-3602.e21. *co-​corresponding
  2. Hir­schen­ber­ger M#, Hunszin­ger V#, Spar­rer KMJ. Impli­ca­ti­ons of Innate Immu­nity in Post-​Acute Seque­lae of Non-​Persistent Viral Infec­tions. Cells. 2021 Aug 19;10(8):2134. # co-​first
  3. Prelli Bozzo C#, Nchioua R#, Volcic M, Koepke L, Krü­ger J, Schütz D, Hel­ler S, Stür­zel CM, Kmiec D, Con­zel­mann C, Mül­ler J, Zech F, Braun E, Groß R, Wett­stein L, Weil T, Weiß J, Dio­fano F, Rodríguez Alfonso AA, Wiese S, Sau­ter D, Münch J, Gof­finet C, Cata­nese A, Schön M, Boeckers TM, Sten­ger S, Sato K, Just S, Kle­ger A, Spar­rer KMJ*, Kirch­hoff F*. IFITM pro­te­ins pro­mote SARS-​CoV-2 infec­tion and are tar­gets for virus inhi­bi­tion in vitro. Nat Com­mun. 2021 Jul 28;12(1):4584. *co-​corresponding
  4. Koepke L#, Hir­schen­ber­ger M#, Hayn M#, Kirch­hoff F, Spar­rer KM. Mani­pu­la­tion of auto­phagy by SARS-​CoV-2 pro­te­ins. Auto­phagy. 2021 Sep;17(9):2659-2661.  # co-​first
  5. Hayn M#, Hir­schen­ber­ger M#, Koepke L#, Nchioua R, Straub JH, Klute S, Hunszin­ger V, Zech F, Prelli Bozzo C, Aftab W, Chris­ten­sen MH, Con­zel­mann C, Mül­ler JA, Sri­ni­va­sachar Bada­rina­rayan S, Stür­zel CM, Forne I, Sten­ger S, Con­zel­mann KK, Münch J, Schmidt FI, Sau­ter D, Imhof A, Kirch­hoff F, Spar­rer KMJ. Sys­te­ma­tic func­tio­nal ana­ly­sis of SARS-​CoV-2 pro­te­ins unco­vers viral innate immune ant­ago­nists and remai­ning vul­nera­bi­li­ties. Cell Rep. 2021 May 18;35(7):109126. # co-​first
  6. Thoms M#, Bus­chauer R#, Ameis­meier M#, Koepke L, Denk T, Hir­schen­ber­ger M, Kratzat H, Hayn M, Mackens-​Kiani T, Cheng J, Straub JH, Stür­zel CM, Fröh­lich T, Ber­n­ing­hau­sen O, Becker T, Kirch­hoff F, Spar­rer KMJ*, Beck­mann R*. Struc­tu­ral basis for trans­la­tio­nal shut­down and immune eva­sion by the Nsp1 pro­tein of SARS-​CoV-2. Sci­ence. 2020 Sep 4;369(6508):1249-1255. *co-​corresponding. # co-​first


Cur­rent lab mem­bers

Lenn­art Koepke

PhD Stu­dent

2018

Maxi­mi­lian Hir­schen­ber­ger

PhD Stu­dent

2019

Jana-​Romana Fischer

MTA

2021

Susanne Klute

PhD Stu­dent

2020

Vic­to­ria Hunszin­ger

PhD Stu­dent

2020

Helene Hoe­nigs­per­ger

PhD Stu­dent

2021

Den­nis Frei­sem

PhD Stu­dent

2021

Johan­nes Lang

MD Stu­dent

2022

Profilbild von Jun. Prof. Konstantin Sparrer

Jun. Prof. Kon­stan­tin Spar­rer

Junior Group Lea­der

BMBF Nach­wuchs­gruppe Immu­n­o­mod