Biology subjects

Metzger, A.

Publications and source records attributed to Metzger, A..

4 recordsLinked to original sources

bioRxiv2026

From haptic exploration to object perception in 3D

Active touch determines which parts of an object are sampled and therefore which sensory information becomes available for perception. However, little is known about how the three-dimensional geometry of an object guides exploratory hand movements and how the information acquired during exploration contributes to perceptual decisions. Here, we investigated these questions in two experiments in which blindfolded participants explored 3D-printed replicas of bell-peppers while their hand movements were recorded using motion tracking. The task of participants' was to identify the reference object among two comparison objects (target & competitor). In the first experiment, objects were presented in a fixed orientation, whereas in the second, object orientation varied across presentations to disrupt the correspondence between hand configuration and object geometry. We first trained a neural network to predict the spatial distribution of touch directly from three-dimensional surface structure. The model successfully predicted touch locations on previously unseen objects, outperforming a generic spatial exploration prior in both experiments. Geometric analyses revealed that haptic saliency was associated with specific combinations of local surface curvatures rather than simply with the overall magnitude of curvature. We then examined whether the information acquired during exploration could predict subsequent recognition choices, considering global and local surface geometry and potential memory decay of acquired object representations. Models integrating global and local information across the complete exploration reliably identified the objectively correct object and correct participants' choices. In contrast, restricting the comparison to temporally proximal portions of successive explorations reduced objective recognition accuracy but increased correspondence with participants' errors. Overall, our findings suggest that haptic exploration is at least to some extent driven by object-specific geometry, but that the information acquired is not necessarily integrated optimally into perceptual decisions. Instead, memory limitations and potentially incomplete integration may constrain how sampled three-dimensional shape information contributes to recognition.

neuroscience↗

bioRxiv2026

Bivalent bispecific CD28 antibodies reinforce T-cell responsiveness and revert anergy/quiescence in patients treated with bispecific CD3 antibodies

Bispecific T-cell engagers stimulating CD3 (TCEs) rapidly gain momentum in oncological therapy. We report that single-agent TCE-treatment of cancer patients induces T cell hyporesponsiveness including abolished proliferative and lytic capacity. Single-cell RNA-sequencing identified transcriptional features of anergy/quiescence like upregulation of CBLB and BACH2, and suppression of AP 1-dependent activation programs due to isolated provision of T cell signal-1. To restore T cell functionality, we engineered bispecific costimulators (BiCos) which deliver signal-2 via highly efficient bivalent CD28-binding yet maintain strictly target-restricted activity after binding antigens expressed not only by tumor cells but also the extracellular matrix. Preclinical analyses documented that BiCos potentiate efficacy of single-agent TCE treatment with activity exceeding that of univalent Knob-into-Hole CD28-costimulators and revert T cell hyporesponsiveness. In humanized mice, BiCos induced elimination of established tumors in combination with very low doses of TCE. Finally, BiCos reversed molecular hallmark features of quiescence such as high expression of BACH2 and KLF2 in T cells of TCE-treated patients resulting in complete restoration of cellular function, thereby reinstating durable antitumor immunity.

immunology↗

bioRxiv2021

Unsupervised learning of haptic material properties

When touching the surface of an object, its spatial structure translates into a vibration on the skin. The perceptual system evolved to translate this pattern into a representation that allows to distinguish between different materials. Here we show that perceptual haptic representation of materials emerges from efficient encoding of vibratory patterns elicited by the interaction with materials. We trained a deep neural network with unsupervised learning (Autoencoder) to reconstruct vibratory patterns elicited by human haptic exploration of different materials. The learned compressed representation (i.e. latent space) allows for classification of material categories (i.e. plastic, stone, wood, fabric, leather/wool, paper, and metal). More importantly, distances between these categories in the latent space resemble perceptual distances, suggesting a similar coding. We could further show, that the temporal tuning of the emergent latent dimensions is similar to properties of human tactile receptors.

neuroscience↗

bioRxiv2018

LADL: Light-activated dynamic looping for endogenous gene expression control

Mammalian genomes are folded into tens of thousands of long-range looping interactions1,2. The cause and effect relationship between looping and genome function is poorly understood, and the extent to which chromatin loops are dynamic on short time scales remains a fundamental unanswered question. Currently available strategies for loop engineering involve synthetic transcription factors tethered to dCas93,4 or zinc fingers5,6, which are constitutively expressed5,6 or induced on long time scales by the presence of a small molecule3. Here we report a new class of 3-D optoepigenetic tools for the directed rearrangement of 3-D chromatin looping on short time scales using blue light. We create synthetic architectural proteins by fusing the CIBN protein subunit from Arabidopsis thaliana with enzymatically dead Cas9 (dCas9). We target our light-activated dynamic looping system (LADL) to two genomic anchors with CRISPR guide RNAs and engineer their spatial co-localization via light-induced heterodimerization of the cryptochrome 2 (CRY2) protein with dCas9-CIBN. We apply LADL to redirect a stretch enhancer (SE) away from its endogenous Klf4 target gene and to the Zfp462 promoter. Looping changes occur as early as four hours after light induction. Using single molecule RNA FISH, we observe a LADL-induced increase in the total nascent Zfp462 transcripts and the number of Zfp462 alleles expressing simultaneously per cell. Moreover, LADL also increased synchronous Sox2 expression after reinforcement of a known Sox2-SE looping interaction. LADL facilitates loop synchronization across a large population of cells without exogenous chemical cofactors and can enable future efforts to engineer reversible and oscillatory looping on short time scales.

molecular biology↗