לוח שנה משולב

A key goal of synthetic biology is to design novel proteins that fold and function in vivo. A particularly challenging objective would be to produce non-natural proteins that don’t merely generate interesting phenotypes, but which actually provide essential functions necessary to sustain life. Successful design of life-sustaining proteins would be a significant step toward constructing entirely artificial “proteomes.” In initia! l work toward this goal providing activities necessary to sustain the growth of living cells. In some cases, the novel proteins rewire gene regulation. In others, the novel protein sustains cell growth by functioning as in vivo, we have designed large libraries of novel proteins encoded by millions of synthetic genes. Many of these proteins fold into stable 3-dimensional structures; and many bind metals, metabolites, and cofactors. Several of the novel proteins function bona fide enzyme that catalyzes an essential biochemical reaction. These results suggest (i) The molecular toolkit of life need not be limited to sequences that already exist in nature; (ii) Synthetic genomes and artificial proteomes can be built from non-natural sequences; (iii) Construction of alternative lifeforms may soon be possible.

Cellular complexity in the brain has been a central area of study since the birth of cellular neuroscience over a hundred years ago. Several different classification systems have been put forward based on emerging techniques. It is still largely unclear if and how the classification system produced using recent single-cell transcriptomics corresponds to previous classification systems. The interneurons of the hippocampus has been extensively characterised on physiological and morphological basis and we used this classification as a basis to compare single-cell RNA sequencing data from the CA1 hippocampus. We show, using the in situ sequencing technique “pciSeq” that the predictions made from scRNAseq data corresponds existing classification. Furthermore, we leverage the rich data from scRNAseq and combined it with GWAS data from patients to begin to elucidate the cellular origin of genetic heritability of brain disorders. Although many of these disorders are genetically complex it seems that specific and sometimes non-overlapping cell types underlie the ethology of these disorders. For instance we show a largely ignored role of oligodendrocytes in Parkinson’s disease which can be confirmed in patient material. This proves the feasibility to link modern transcriptomics with genetics to leverage the recent advances in understanding of genetic structure of brain disorders to yield actionable targets.