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Informacja o budowie i funkcjonowaniu organizmów żywych zapisana jest w genach. W regulację ekspresji genów zaangażowane są specyficzne czynniki transkrypcyjne, które odpowiedzialne są odbieranie sygnałów płynących z zewnątrz komórki i przekazywanie ich poprzez aktywację transkrypcji odpowiednich zestawów genów. Podczas rozwoju organizmu cząsteczkami sygnałowymi są m.in. hormony, dlatego rozumienie mechanizmów sygnalizacji hormonalnej i zależnej od niej ekspresji informacji genetycznej jest bardzo ważne. Organizmy modelowe stanowią doskonałe źródło wiedzy, która pozwala zrozumieć wiele procesów fizjologicznych zachodzących w organizmie człowieka. Warto podkreślić, że bez żmudnych eksperymentów naukowych przeprowadzanych na organizmach takich jak Drosophila melanogaster, czy Aedes aegypti, nie byłoby możliwe poznanie i zrozumienie sygnalizacji hormonalnej u człowieka. Dogłębne badania szlaku przekazywania sygnałów pochodzących od 20-hydroksyekdyzonu (20E) i hormonu juwenilnego (JH) w obu organizmach pozwalają zrozumieć molekularne i genetyczne podstawy przekazywania sygnałów w organizmach wielokomórkowych, w tym sposobu, w jaki cząsteczki sygnałowe kierują rozwojem zarodka od pojedynczej komórki do dojrzałego organizmu.

Viruses rely on the reprogramming of cellular processes to enable efficient viral replication; this often requires subcompartmentalization within the host cell. Liquid-liquid phase separation (LLPS) has emerged as a fundamental principle to organize and subdivide cellular processes, and plays an important role in viral life cycles. Despite substantial advances in the field, elucidating the exact organization and function of these organelles remains a major challenge. In this review, we summarize the biochemical basis of condensate formation, the role of LLPS during viral infection, and interplay of LLPS with innate immune responses. Finally, we discuss possible strategies and molecules to modulate LLPS during viral infections.

One of the main structural proteins of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the nucleocapsid protein (N). The basic function of this protein is to bind genomic RNA and to form a protective nucleocapsid in the mature virion. The intrinsic ability of the N protein to interact with nucleic acids makes its purification very challenging. Therefore, typically employed purification methods appear to be insufficient for removing nucleic acid contamination. In this study, we present a novel purification protocol that enables the N protein to be prepared without any bound nucleic acids. We also performed comparative structural analysis of the N protein contaminated with nucleic acids and free of contamination and showed significant differences in the structural and phase separation properties of the protein. These results indicate that nucleic-acid contamination may severely affect molecular properties of the purified N protein. In addition, the notable ability of the N protein to form condensates whose morphology and behaviour suggest more ordered forms resembling gel-like or solid structures is described.

The bHLH-PAS proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, from differentiation and development control, by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for their activity regulation. Our aim was to analyse the potential connection between disordered regions of the bHLH-PAS transcription factors with posttranscriptional modifications and liquid-liquid phase separation in the context of the disease-associated missense mutations. Highly flexible disordered regions, enriched in short more ordered motives, are responsible for wide spectrum of interactions with transcriptional co-regulators. Based on our in silico analysis and taking into account fact that transcription factors functions can be modulated by posttranslational modifications and spontaneous phase separation, we assume that the location of missense mutations inducing disease states, is clearly related to sequences directly undergoing these processes or to sequences responsible for their activity regulation.

The basic helix–loop–helix/Per-ARNT-SIM (bHLH-PAS) proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, ranging from differentiation and development control by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for regulation of their activity. Our aim was to analyze the potential connection between disordered regions of the bHLH-PAS transcription factors, post-transcriptional modifications and liquid-liquid phase separation, in the context of disease-associated missense mutations. Highly flexible disordered regions, enriched in short motives which are more ordered, are responsible for a wide spectrum of interactions with transcriptional co-regulators. Based on our in silico analysis and taking into account the fact that the functions of transcription factors can be modulated by posttranslational modifications and spontaneous phase separation, we assume that the locations of missense mutations inducing disease states are clearly related to sequences directly undergoing these processes or to sequences responsible for their regulation.